1. 内脏脂肪的生理特性与健康影响
1.1 内脏脂肪的定义与分布特征
内脏脂肪（Visceral Adipose Tissue, VAT）特指积聚在腹腔内脏器周围的脂肪组织，例如肠系膜、大网膜和肾脏周围的脂肪垫等1。它与皮下脂肪（Subcutaneous Adipose Tissue, SAT）在解剖学定位和生理功能上存在显著差异。皮下脂肪主要分布在皮肤下方，而内脏脂肪则深藏于腹腔内部1。这种解剖位置的差异赋予了内脏脂肪独特的代谢特征。
内脏脂肪的一个关键生理属性是其通过门静脉系统直接影响肝脏代谢。内脏脂肪分解产生的游离脂肪酸（Free Fatty Acids, FFAs）不经过体循环，而是直接通过门静脉系统进入肝脏。相比之下，皮下脂肪分解产生的FFAs则首先进入全身循环。这种“门静脉假说”认为，高水平的内脏脂肪FFAs直接暴露于肝脏，可能导致肝脏胰岛素抵抗、肝脏脂肪堆积（如非酒精性脂肪性肝病，NAFLD）以及异常的脂蛋白合成和分泌23。尽管有研究指出，在肥胖个体中，上半身皮下脂肪对全身FFAs的贡献最大，但内脏脂肪FFAs仍对肝脏有更直接的影响3。
从细胞层面看，人类脂肪组织具有功能上的区分性，皮下脂肪和内脏脂肪库虽然存在重叠或相似的细胞类型，但其细胞组成、分化轨迹和细胞间通讯模式仍有不同4。内脏脂肪组织中的脂肪细胞大小、数量、脂解反应性、脂质储存能力以及炎症细胞因子产生等特性，都与内脏肥胖相关的代谢心脏风险增加密切相关2。过度摄入饱和脂肪酸（SFAs）会促进肝脏和内脏脂肪的储存，而多不饱和脂肪酸（PUFAs）则可能促进瘦体组织的增加5。此外，内脏脂肪组织的功能障碍（如慢性低度炎症）是导致代谢疾病进展的机制之一，并与肥胖和衰老过程中的白色脂肪组织改变密切相关6。
1.2 内脏脂肪堆积的健康风险
内脏脂肪（VAT）的过度堆积被认为是多种慢性疾病的“门户”，对人体健康构成多系统、全方位的威胁 7。其致病机制复杂，涉及内分泌、代谢和免疫等多个层面。
1.2.1 代谢综合征
内脏脂肪过量是代谢综合征（Metabolic Syndrome, MetS）的核心组成部分和关键驱动因素 8。代谢综合征是一系列心血管疾病、2型糖尿病及其他健康问题可改变的风险因素的集合 8。内脏脂肪的蓄积通过多种途径导致代谢紊乱：
- 胰岛素抵抗： 内脏脂肪组织功能异常，会释放更多的游离脂肪酸（FFAs）和促炎细胞因子（如IL-6、TNF-α），这些物质直接进入门静脉循环，高浓度地作用于肝脏，诱导肝脏和外周组织的胰岛素抵抗 910。胰岛素抵抗是2型糖尿病发生发展的基础。
- 血脂异常： 代谢综合征的诊断通常关注腹部肥胖（通过腰围评估）、高血糖、血脂异常和高血压 8。激活法尼醇X受体（FXR）可降低血浆甘油三酯水平，这可能涉及抑制肝脏SREBP-1c表达或调节葡萄糖诱导的脂肪生成基因 11。
- 高血压： 代谢综合征的诊断标准之一就是血压升高 8。代谢综合征与高血压相关联 12。
- 慢性炎症： 肥胖，尤其是内脏脂肪肥胖，导致脂肪组织内慢性低度炎症的发生 613。肥胖个体的循环炎症细胞因子（如IL-6、TNF-α、CRP、IL-18、抵抗素和内脏脂肪素）水平升高 10。这些炎症因子不仅加剧胰岛素抵抗，还参与动脉粥样硬化等心血管疾病的病理过程。
有研究指出，腰围作为内脏脂肪堆积的良好指标，在评估代谢紊乱风险方面优于体重指数（BMI） 710。针对中国人群的内脏肥胖指数（CVAI）也被证明是评估代谢健康状况的可靠指标，其预测代谢综合征、高血压、糖尿病和糖尿病前期的曲线下面积（AUROC）分别为0.89、0.72、0.69和0.67，甚至在代谢不健康的正常体重和代谢健康的超重/肥胖个体中也具有价值 14。
1.2.2 非酒精性脂肪性肝病 (NAFLD)
NAFLD与内脏脂肪堆积之间存在着紧密的双向关系。内脏脂肪的过量分解是肝脏脂肪变性的主要原因之一，因为FFAs直接通过门静脉进入肝脏，导致肝脏脂质积累 9。NAFLD的严重程度从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH），进而发展为肝硬化甚至肝癌。NAFLD不仅是肝脏疾病，也是全身性疾病，与心血管疾病、2型糖尿病、慢性肾病等多种并发症密切相关 151617。生物信息学分析和孟德尔随机化研究发现，NAFLD与心力衰竭之间存在双向因果关系，突出了它们之间复杂的相互作用 15。
1.2.3 心血管疾病
内脏脂肪，特别是心外膜脂肪（Epicardial Adipose Tissue, EAT），被认为是一种独特的内脏脂肪储存库，与心血管健康，特别是心血管疾病（CVDs）密切相关 18。EAT直接毗邻心脏，其功能障碍可导致局部炎症、氧化应激和细胞因子释放，直接影响心肌功能和冠状动脉粥样硬化的发生发展 19。内脏脂肪堆积与冠心病、心力衰竭的风险增加呈正相关 151617。研究表明，一些免疫炎症生物标志物，如中性粒细胞-高密度脂蛋白比率（NHR）、中性粒细胞-淋巴细胞比率（NLR）等，在NAFLD患者中与冠心病风险显著相关，其中NHR指数显示出良好的预测潜力 20。
1.2.4 慢性炎症与全身性影响
除了上述疾病，内脏脂肪引起的慢性低度炎症还与多种健康问题相关：
- 慢性肾病： 代谢综合征，其中内脏肥胖是关键组分，与慢性肾病的发生和进展密切相关。内脏脂肪释放的促炎因子和FFAs可导致肾脏结构和功能损伤，包括肾小球病变 12。
- 癌肿： 慢性炎症被认为是癌症发生发展的驱动因素之一，内脏脂肪诱导的炎症环境可能增加某些癌症的风险 10。
- 肌少症性肥胖： 衰老会引起身体成分的改变，如内脏脂肪增加和肌肉量减少。肌少症性肥胖（Sarcopenic Obesity）是肌少症和肥胖的结合，内脏脂肪过量会加速肌肉质量和力量的下降，从而增加心血管代谢疾病的死亡风险 21。
- 特发性肺纤维化 (IPF)： 研究表明，内脏脂肪沉积与IPF的严重程度、生活质量、合并症和总体预后相关，可能通过介导炎症和氧化应激促进肺损伤和纤维化 22。
综上所述，内脏脂肪的过量堆积及其功能障碍是导致代谢综合征、NAFLD、心血管疾病、慢性炎症等一系列健康问题的核心因素。因此，有效管理和减少内脏脂肪对于维护整体健康具有至关重要的意义。
2. 内脏脂肪堆积的关键驱动因素
2.1 激素与年龄相关机制
内脏脂肪的堆积并非单一因素所致，而是多种生理学和生物化学过程共同作用的结果，其中激素水平的变化和年龄增长扮演着关键角色。
2.1.1 绝经后雌激素水平下降的影响
女性在绝经后面临内脏脂肪显著增加的风险。这主要归因于雌激素水平的急剧下降和循环雄激素的相对增加 23。雌激素在调节食欲、饮食行为和能量代谢中发挥着重要作用 24。在绝经前，雌激素有助于维持脂肪在皮下（特别是臀部和大腿）的分布，而绝经后雌激素的减少则会导致脂肪从外周向中心重新分布，表现为内脏脂肪的优先堆积 22325。这种脂肪分布的改变使得绝经后女性更容易出现腹部肥胖和相关的代谢紊乱 232426。
雌激素对脂肪组织代谢的影响机制复杂。雌激素可能通过改变脂肪细胞的雌激素受体分布（ERα/ERβ比例）及其后续的代谢信号通路来调节脂肪组织积累 27。例如，雌激素可影响脂肪细胞的脂质和葡萄糖代谢，导致脂肪形成增加、脂肪分解减少、线粒体功能受损等 27。在绝经后女性的内脏脂肪组织中，雌激素和雄激素的局部浓度及其代谢过程也发生了显著变化 2526。研究发现，绝经后女性的皮下和内脏脂肪组织中雌酮和雌二醇的浓度高于循环水平 26。口服激素替代疗法（HT）可以显著提高皮下和内脏脂肪中的雌酮和雌二醇浓度，并降低内脏脂肪中的睾酮水平，从而提高局部雌激素与雄激素的比率，这可能有助于预防与绝经相关的腹部肥胖 25。然而，对于老年绝经后女性，雌激素补充剂可能通过靶向IGF2BP1恶化内脏脂肪功能，导致促炎细胞因子增加和胰岛素敏感性降低 28。
此外，绝经后女性体内骨髓源性脂肪细胞的增加，也与雌激素丧失导致的内脏脂肪增加有关 23。雌激素的减少还会导致参与β-氧化（脂肪酸分解代谢）的基因下调，使得内脏脂肪脂解产生的过量游离脂肪酸不能被有效利用，从而加剧脂肪积累 23。
2.1.2 年龄增长导致的脂肪祖细胞活化与脂肪生成增强
衰老是一个复杂的生物学过程，伴随着身体成分的显著变化，包括内脏脂肪的增加和皮下脂肪的减少 29。在成年中期开始，许多人会经历内脏脂肪的堆积及相关的代谢紊乱 30。这背后一个重要的分子机制是脂肪祖细胞（Adipose Progenitor Cells, APCs）的改变。
小鼠模型中的谱系追踪研究显示，在中年时期，内脏脂肪中的APCs会进行广泛的脂肪生成（adipogenesis）30。这意味着，尽管年轻成年人的脂肪细胞更新率较低，但在中年时期，脂肪生成过程被“解锁”并增强 30。移植实验定量表明，中年小鼠的APCs细胞自主地表现出高脂肪生成能力 30。
单细胞RNA测序技术进一步揭示了一个独特的APCs群体，即“特异性前脂肪细胞，年龄富集型”（committed preadipocyte, age-enriched, CP-A），在这一年龄段出现并增多 30。CP-As表现出更高的增殖和脂肪生成活性 30。药理学和遗传学干预研究表明，白血病抑制因子受体（Leukemia Inhibitory Factor Receptor, LIFR）信号通路对CP-A的脂肪生成和内脏脂肪扩张至关重要 30。这些发现揭示了年龄依赖性脂肪重塑的一个基本机制，为理解与年龄相关的代谢疾病提供了关键见解 30。
此外，脂肪组织中的多能祖细胞/干细胞在维持组织健康和修复中发挥着关键作用，但其质量会受到年龄、BMI、疾病状态以及性别和种族等因素的影响 31。衰老还会改变脂肪组织的免疫微环境，例如，调节性T细胞（Treg细胞）在表皮附睾内脏脂肪组织（eVAT）中通过调节基质脂肪细胞前体的分化来维持代谢稳态，但其功能可能随年龄变化 32。在衰老过程中，皮下脂肪中还可能出现一种“年龄依赖性调节细胞”（Aging-dependent Regulatory Cell, ARC），这些细胞表达脂肪祖细胞标志物，但缺乏脂肪生成能力，并分泌促炎趋化因子抑制附近脂肪前体的增殖和分化，从而导致皮下脂肪的减少 33。这进一步凸显了不同脂肪组织库在衰老过程中表现出的异质性及其对全身代谢的不同影响。
2.2 饮食与生活方式的作用
内脏脂肪的堆积与现代饮食习惯和生活方式密切相关。高热量饮食，特别是富含果糖和饱和脂肪的食物，以及久坐不动的生活方式，是促进内脏脂肪积累的主要驱动因素。肠道菌群失调在这一过程中扮演着重要的中介角色。
2.2.1 高热量饮食的影响
- 果糖摄入： 大量摄入果糖是内脏脂肪堆积和非酒精性脂肪性肝病（NAFLD）的重要风险因素34。果糖在肝脏中代谢，过量果糖迅速转化为脂肪，促进肝脏和内脏脂肪的生成。高果糖饮食可能导致肝脏脂肪含量升高，并诱发胰岛素抵抗3435。
- 饱和脂肪与反式脂肪： 富含饱和脂肪（SFAs）和反式脂肪（TFAs）的饮食对内脏脂肪堆积具有显著的促进作用。饱和脂肪酸已被证明会增加肝脏脂肪含量和胰岛素抵抗3536。反式脂肪酸（TFA）的摄入会增强肝脏中甘油-3-磷酸酰基转移酶1 (GPAM) 的表达，进而促进肝脏脂肪沉积并减少内脏脂肪组织，这表明反式脂肪酸可能通过特定的分子机制影响脂肪分布，提示膳食脂肪酸组成对MASLD（代谢功能障碍相关脂肪性肝病）发病机制的影响37。此外，高脂肪饮食，特别是饱和脂肪，能够改变肠道菌群组成，导致炎症反应和代谢紊乱38。
- 整体能量过剩： 任何形式的长期能量摄入过剩，无论是来自碳水化合物还是脂肪，都会导致体重增加和脂肪堆积，其中包括内脏脂肪。研究显示，即使是等热量饮食，不同脂肪酸组成（如饱和脂肪与多不饱和脂肪）也会对肝脏脂肪积累产生不同影响3536。短期低热量饮食能有效减少肝脏脂肪含量，且任何形式的卡路里限制都可能长期有效3435。
2.2.2 久坐行为的影响
久坐行为是现代社会普遍存在的生活方式，与内脏脂肪堆积呈正相关。多项研究发现，长时间的久坐行为与内脏脂肪面积（VFA）的增加显著相关39。例如，一项针对日本成年人的纵向研究发现，与2018年相比，2020年（新冠疫情期间）受试者的久坐行为和内脏脂肪面积均显著增加，而脂联素水平显著降低。久坐行为的增加与内脏脂肪面积的增加独立相关39。另一项研究也指出，较高的久坐时间与较差的睡眠质量相关，即使在调整了内脏脂肪量等因素后，这种关联仍然存在40。尽管有研究发现客观测量的偶发性体力活动和久坐行为与不活动成年人的腹部脂肪组织无关41，但大多数证据支持久坐是内脏脂肪堆积的风险因素。
久坐行为可能通过减少能量消耗、影响脂质代谢和胰岛素敏感性，进而促进内脏脂肪的积累。缺乏体力活动不仅直接导致脂肪堆积，还可能通过影响肠道菌群，间接促进内脏脂肪的增加。
2.2.3 肠道菌群失调的中介机制
肠道菌群在调节宿主能量代谢和脂肪分布中发挥着关键作用。不健康的饮食和生活方式会破坏肠道菌群的平衡，导致肠道菌群失调（Dysbiosis），进而促进内脏脂肪的堆积：
- 短链脂肪酸（SCFAs）减少： 肠道菌群对膳食纤维的酵解产生短链脂肪酸（如丁酸、丙酸、乙酸）。SCFAs是肠道细胞的重要能量来源，并具有抗炎作用。高脂肪饮食（HFD）或高脂肪高胆固醇饮食（HFHCD）可显著降低盲肠中短链脂肪酸的含量42。短链脂肪酸（如丁酸）被发现可以增加内脏脂肪中的ST2调节性T细胞数量，改善葡萄糖耐受和内脏炎症，表明肠道菌群-丁酸-PPARγ轴在维持内脏脂肪Treg细胞群中的关键作用43。丁酸及其甘油三酯形式（丁酸甘油三酯）能够显著减少脂多糖（LPS）诱导的人体内脏脂肪组织炎症细胞因子和趋化因子的产生4445。这些结果提示，短链脂肪酸的减少可能削弱其对内脏脂肪炎症和堆积的抑制作用。
- 炎症因子释放与肠道屏障功能受损： 肠道菌群失调可导致肠道通透性增加（“肠漏”），使得细菌产物（如脂多糖LPS）易位进入血液循环和门静脉系统38。这些细菌产物会触发全身性炎症反应，并在内脏脂肪组织中引起慢性低度炎症。有研究表明，肥胖个体中内脏脂肪组织含有更多的中性粒细胞，并与独特的细菌群落相关。移植来自肥胖个体的粪便可导致高脂肪饮食小鼠内脏脂肪中中性粒细胞增多，提示供体微生物组和受体饮食共同决定内脏脂肪中性粒细胞的产生，从而引发炎症46。这种炎症是胰岛素抵抗和多种代谢疾病的重要驱动因素。
- 特定菌群的变化： 高脂肪饮食会显著改变肠道菌群的组成。例如，高脂肪饮食会减少乳酸杆菌属和双歧杆菌属等益生菌，同时增加某些促炎菌群。低脂纯素饮食能够改变肠道菌群，增加粪杆菌属（Faecalibacterium prausnitzii）的相对丰度，这与体重、脂肪量和内脏脂肪的减少呈负相关，并改善胰岛素敏感性47。绿原酸通过增加产短链脂肪酸的细菌（如厚壁菌门、拟杆菌门、瘤胃球菌科和乳酸杆菌科）以及Akkermansia muciniphila的丰度来改善代谢性内毒素血症，这提示特定的菌群变化与内脏脂肪代谢的改善有关48。
综上所述，不健康的饮食和久坐的生活方式不仅直接导致能量过剩和脂肪堆积，还通过改变肠道菌群的组成和功能，诱发炎症反应和代谢紊乱，从而共同促进内脏脂肪的过度积累。
2.3 遗传与环境交互影响
内脏脂肪的堆积不仅受激素、年龄、饮食和生活方式的直接影响，遗传因素与环境因素之间的复杂交互作用也在此过程中扮演着至关重要的角色，解释了个体间内脏脂肪堆积的显著差异。
2.3.1 遗传易感性
遗传因素对人体脂肪分布，特别是内脏脂肪量，具有显著影响。双生子研究显示，遗传因素对心外膜脂肪组织（EAT）、腹部皮下脂肪组织（SAT）和内脏脂肪组织（VAT）的体积贡献度分别为80%、78%和70% 49。这表明，虽然环境因素有一定影响，但遗传背景在决定个体脂肪储存模式中占主导地位。
多个基因位点与内脏脂肪的堆积相关。例如，研究发现日本人群中与肥胖相关的基因变异，尤其是那些影响内脏脂肪堆积的基因，可能在进化过程中受到自然选择的影响，以适应节俭基因型 50。欧洲人群中的研究也通过全基因组关联研究（GWAS）发现了与内脏脂肪相关的基因座。此外，有研究通过整合脂肪和肝脏的单细胞RNA测序数据和bulk cis-expression定量性状基因座（eQTL）数据，结合英国生物银行（UK Biobank）的GWAS数据，发现了17个与腹部肥胖相关的细胞类型特异性基因 51。这些基因在脂肪细胞中的表达富集，并且敲低其中两个基因（PPP2R5A和SH3PXD2B）能够显著减少脂肪细胞脂质化，并改变脂肪细胞功能和脂肪生成调节基因的表达，表明它们在脂肪生成中发挥作用 51。
2.3.2 环境因素的协同作用
尽管遗传因素提供了内脏脂肪堆积的“蓝图”，但环境因素则决定了这一蓝图如何被“执行”。
孕期营养： 母亲在孕期的营养状况对后代内脏脂肪的堆积有长期影响。孕期营养不良或营养过剩都可能通过表观遗传机制，影响胎儿的代谢编程，使其成年后更容易发展为内脏肥胖和相关的代谢性疾病 52。这种“发育起源健康与疾病”（DOHaD）理论强调了早期生命阶段环境暴露的重要性。
睡眠不足： 睡眠质量和时长与内脏脂肪的累积密切相关。睡眠不足或昼夜节律紊乱已被证明会干扰食欲调节激素（如瘦素和生长素释放肽）的分泌，增加饥饿感和能量摄入，从而促进脂肪堆积 53。一项针对美国国家健康与营养检查调查（NHANES）数据的研究发现，较高的内脏脂肪指数（VAI）与阻塞性睡眠呼吸暂停（OSA）的风险增加呈正相关，提示睡眠障碍与内脏脂肪之间存在复杂的关联 54。此外，睡眠不足还会影响减重期间脂肪量的减少，以及脂肪的氧化 53。
慢性心理社会压力： 慢性心理社会压力被认为是许多疾病（包括肥胖）发展的重要风险因素。神经肽Y（NPY）在应激和肥胖之间的病理生理关系中发挥作用。研究发现，NPY基因多态性与心理社会压力之间存在显著的交互作用，共同影响包括内脏脂肪组织（VAT）在内的肥胖相关性状。在携带纯合风险等位基因的个体中，应激水平的增加导致VAT的平均变化最大，强调了应激管理在肥胖预防中的重要性 55。
饮食质量： 饮食质量的改善与腹部和心包脂肪的长期减少有关。地中海饮食评分（MDS）每提高一个标准差，内脏脂肪（VAT）的积累减少50 cm³，腹部皮下脂肪（SAT）减少52 cm³，心包脂肪（PAT）减少1.3 cm³ 56。这表明，即使在有遗传易感性的个体中，良好的饮食习惯也能有效减轻内脏脂肪的堆积 56。
微生物组： 肠道微生物组是环境因素的重要组成部分，其与宿主遗传背景和饮食习惯相互作用，影响能量代谢和脂肪分布。不健康的饮食模式（如高脂饮食）可导致肠道菌群失调，进而影响内脏脂肪的堆积和相关的炎症反应。
综上所述，内脏脂肪的堆积是个体遗传倾向与多种环境因素（如孕期营养、睡眠、压力和饮食）协同作用的结果。理解这些交互机制有助于制定更精准的个体化干预策略。
3. 生活方式干预：减控内脏脂肪的核心策略
生活方式干预是减少内脏脂肪（VAT）并改善相关代谢健康的基石，它通过调整饮食结构、增加体育活动和优化行为习惯来发挥作用。
3.1 饮食调控的优化方案
饮食是影响内脏脂肪积累和代谢健康的最主要因素之一。不同的饮食模式对内脏脂肪的影响各异，且其效果可能受到多种因素（如性别、年龄、初始体重状况等）的影响。
3.1.1 不同饮食模式对内脏脂肪的影响
时间限制饮食 (Time-Restricted Eating, TRE)： TRE是一种间歇性禁食的形式，通过将每日的能量摄入限制在特定的时间窗口内，例如8小时的进食窗口，其余时间禁食。多项研究表明，TRE有助于减少体重、体脂和内脏脂肪。一项针对超重老年男性和女性（65-74岁）的研究发现，为期六周的16/8 TRE干预显著降低了受试者的体重，其中男性内脏脂肪量显著减少0.54升（p ≤ 0.001）和腰围减少2.9厘米（p ≤ 0.015），而女性体重有所下降，但内脏脂肪或腰围没有显著变化 57。这提示TRE对不同性别个体效果可能存在差异。另一项针对超重女性的随机对照试验也发现，结合阻力训练的TRE和高蛋白饮食显著减少了内脏脂肪（p < 0.001），且高蛋白组的去脂体重有所增加 58。然而，也有研究指出，结合低碳水化合物饮食的隔日禁食（ADF-LC）方案，尽管能有效减轻体重和脂肪量，但在6个月的干预期间，内脏脂肪没有显著变化 59。一项正在进行中的研究协议旨在进一步探究8小时TRE的不同时间安排（如早期、晚期、自由选择）对内脏脂肪和心血管代谢健康的影响 60。
地中海饮食 (Mediterranean Diet, Md)： 地中海饮食是一种以植物性食物、全谷物、鱼类、橄榄油为主，限制红肉和加工食品的健康饮食模式。它因其抗炎和抗氧化特性，被广泛推荐用于心血管疾病和代谢综合征的预防和管理 6162。多项研究证实，地中海饮食对减少内脏脂肪具有积极作用。一项随机临床试验表明，基于地中海饮食的限能量饮食（能量减少）结合体力活动，能显著减少超重或肥胖且伴有代谢综合征的中老年人的总脂肪和内脏脂肪储存，并减缓与年龄相关的去脂体重丢失 63。另一项针对炎症性肠病（IBD）患者的研究也发现，为期六个月的地中海饮食显著改善了体重指数（BMI）和腰围，并减少了肝脏脂肪变性，这间接提示了其对内脏脂肪的潜在益处 64。此外，一项针对心血管疾病高风险个体的随机临床试验显示，结合体育锻炼的地中海饮食显著降低了腰围、身体总脂肪和内脏脂肪，并增加了豆类摄入量和对地中海饮食的依从性，后者与腰围和内脏脂肪的减少相关 65。地中海饮食通过降低甘油三酯和低密度脂蛋白胆固醇、升高高密度脂蛋白胆固醇、调节血糖水平，并促进体重减轻和身体成分改善（特别是减少内脏脂肪），全面改善代谢综合征的各组成部分 62。
低热量饮食 (Low-Calorie Diet, LCD) 和极低热量生酮饮食 (Very Low-Calorie Ketogenic Diet, VLCKD)： 总体而言，能量限制是减少内脏脂肪的关键策略。研究表明，与标准低热量饮食相比，极低热量生酮饮食在减少内脏脂肪和肝脏脂肪方面表现出更优异的效果。一项随机对照研究比较了VLCKD和标准低热量饮食对肥胖患者内脏和肝脏脂肪积累的影响，结果发现，VLCKD组的体重减轻幅度更大（-9.59% vs -1.87%），内脏脂肪平均减少量显著高于LC组（-32.0 cm³ vs -12.58 cm³，p < 0.05），肝脏脂肪分数也显著下降（4.77% vs 0.79%，p < 0.005） 66。这表明VLCKD在快速动员肝脏脂肪和减少内脏脂肪方面可能更有效。另一项针对牛皮癣和银屑病关节炎合并肥胖患者的交叉随机试验也发现，生酮饮食相比地中海饮食，能更显著地减少体重、BMI、腰围、总脂肪量和内脏脂肪 67。然而，需要注意的是，极低热量生酮饮食可能对记忆造成损害，并在氧化应激水平上表现出损伤 68。
低碳水化合物饮食 (Low-Carbohydrate Diet, LCD)： 低碳水化合物饮食，特别是当与限时进食结合时，被认为对内脏脂肪有益。一项研究表明，结合低碳水化合物饮食的隔日禁食方案虽然没有显著改变内脏脂肪，但有效减轻了体重和脂肪量 59。在老年群体中，间歇性禁食结合低碳水饮食或高蛋白饮食，可以有效减少内脏脂肪，并维持肌肉质量。
3.1.2 限时进食联合低碳水饮食的协同效应
虽然单一的限时进食或低碳水化合物饮食都有减少内脏脂肪的潜力，但将两者结合起来，可能会产生协同效应，进一步优化内脏脂肪的减控及代谢指标的改善。限时进食通过限制进食时间窗口，减少了总能量摄入，并可能通过调节昼夜节律来改善代谢健康。低碳水化合物饮食则侧重于减少碳水化合物摄入，促使身体进入脂肪燃烧模式，从而减少脂肪储存。
例如，一项将TRE与高蛋白饮食（其中通常包含相对较低的碳水化合物）结合的研究，在超重女性中显示出显著的内脏脂肪减少和去脂体重的保留 58。此外，斋月期间的间歇性禁食（一种形式的TRE）被发现可以减少健康个体的卡路里摄入，并显著降低体重、BMI、腰围、皮下和内脏脂肪厚度以及胰岛素抵抗，同时改善胃肠蠕动和症状 69。这表明，结合了能量限制和特定宏量营养素组成的饮食模式，能够多方面促进内脏脂肪的减少和整体代谢健康。
总之，饮食干预是减控内脏脂肪的核心策略之一。尽管地中海饮食因其全面益处而受到推崇，但针对个体情况，如需要快速减重和减少内脏脂肪，极低热量生酮饮食也显示出良好效果。而限时进食作为一种可行的策略，与低碳水化合物饮食结合时，可能在减少内脏脂肪方面提供协同优势，但仍需更多研究来明确其长期效果和适用人群。
3.2 运动干预的类型与剂量
运动是减少内脏脂肪（VAT）和改善整体代谢健康最有效且安全的手段之一 7071。不同类型的运动，包括有氧运动、抗阻训练以及两者结合的组合运动，对内脏脂肪的消耗机制和效果存在差异。
3.2.1 有氧运动对内脏脂肪的选择性消耗机制
有氧运动，如跑步、骑自行车、游泳等，通过长时间、中等强度的持续运动来提高心率和呼吸频率，从而促进脂肪氧化，消耗能量。研究表明，有氧运动能显著减少内脏脂肪，其机制可能包括：
- 能量消耗和脂肪动员： 有氧运动直接增加能量消耗，促使身体动员储存的脂肪作为燃料，尤其是内脏脂肪对运动引起的脂解反应更为敏感 72。
- 改善胰岛素敏感性： 有氧运动能显著提高胰岛素敏感性，降低胰岛素抵抗。运动后葡萄糖摄取在一定程度上独立于胰岛素作用，可能涉及GLUT4转运蛋白向细胞膜的转运增加 73。长期规律的有氧运动可引发肌肉中葡萄糖转运和代谢的多种适应性改变，并改善肝脏葡萄糖输出的调节，这对于胰岛素抵抗的治疗和预防至关重要 73。此外，运动能减少脂肪因子（如瘦素）的异常分泌，并改善胰岛素信号转导通路 74。
- 抗炎作用： 运动可诱导细胞因子（如IL-6、IL-10）的释放，这些细胞因子具有直接的抗炎作用，通过抑制促炎细胞因子（如TNF-α、IL-1β）的活性来改善慢性低度炎症状态 75。有氧运动通过调节血管平滑肌细胞（VSMC）的表型，缓解高脂肪饮食诱导的内脏脂肪组织炎症，从而改善胰岛素抵抗 72。
- 线粒体功能改善： 有氧运动可以改善线粒体功能，提高脂肪酸β-氧化能力，从而促进脂肪消耗并减少异位脂肪沉积 76。
高强度间歇训练（HIIT）作为一种特殊形式的有氧运动，在减少内脏脂肪方面表现出显著优势。Meta分析显示，HIIT能有效减少总脂肪、腹部脂肪和内脏脂肪 7778。跑步形式的HIIT在减少腹部脂肪方面可能优于骑行形式的HIIT 79。一项针对肥胖青少年男性的研究发现，HIIT组内脏脂肪显著减少，且心肺适能改善幅度大于中等强度持续训练组 80。
3.2.2 抗阻训练对内脏脂肪的作用机制
抗阻训练（Resistance Training, REX），如举重、使用器械进行力量训练，主要通过增加肌肉量和提高基础代谢率来影响内脏脂肪：
- 增加肌肉量： 抗阻训练能够有效增加骨骼肌质量。肌肉是葡萄糖消耗的主要场所，肌肉量的增加意味着葡萄糖摄取能力的增强，从而改善胰岛素敏感性。
- 抑制脂肪合成： 在卵巢切除大鼠模型中，抗阻训练通过抑制内脏脂肪酸合成和增强脂肪酸β-氧化来减少腹腔内脂肪组织（intra-AAT）脂肪细胞的大小，从而预防卵巢激素丧失引起的内脏脂肪增加 81。
- 改善炎症和胰岛素抵抗： 抗阻训练能显著改善肥胖大鼠的脂肪肝、胰岛素抵抗和炎症生物标志物，降低体重、脂肪垫、甘油三酯、总胆固醇、葡萄糖、瘦素和肿瘤坏死因子-α（TNF-α）水平 82。
- 直接减少脂肪： 尽管传统观点认为抗阻训练对脂肪消耗的直接作用不如有氧运动，但越来越多的证据表明，抗阻训练也能直接减少脂肪量，包括内脏脂肪 82。
3.2.3 组合运动在老年肥胖人群中的应用与效果
老年肥胖人群常常面临肌肉量减少（肌少症）和内脏脂肪增加的双重困扰，即肌少性肥胖。针对这类人群，单一的有氧或抗阻训练可能无法达到最佳效果，而组合运动（有氧运动与抗阻训练结合）则显示出更全面的益处。
一项针对老年肥胖人群的随机对照试验比较了有氧运动（AEX）、抗阻训练（REX）和组合运动（COMB）在匹配约10%体重减轻情况下的效果。结果显示，与AEX和REX组相比，COMB组的肌间脂肪组织（IMAT）和内脏脂肪组织（VAT）减少更多（IMAT：-41% vs -28%和-23%；VAT：-36% vs -19%和-21%），胰岛素敏感性指数（ISI）改善也更显著（86% vs 50%和39%） 83。此外，COMB组在体力功能（PPT）、最大摄氧量（VO2peak）和膝关节力量方面也显示出更优异的改善 83。这些结果强调了组合运动在老年肥胖人群中，通过同时减少内脏脂肪、改善胰岛素敏感性、提升肌肉力量和心肺功能，来综合干预肌少性肥胖的优势。
太极拳作为一种融合有氧和抗阻成分的传统运动，也被证明对中老年中心性肥胖人群具有积极作用。一项研究显示，太极拳组和常规运动组（有氧运动+力量训练）在12周后均显著减少了腰围和体重，且这种益处在38周后仍能维持，太极拳组对高密度脂蛋白胆固醇的益处甚至维持得更好 84。这表明温和的组合运动形式也能有效干预内脏脂肪。
综上所述，运动是减控内脏脂肪不可或缺的策略。有氧运动通过直接消耗脂肪和改善胰岛素敏感性来发挥作用，而抗阻训练则侧重于增加肌肉量和提高基础代谢率。对于老年肥胖人群，组合运动能提供更全面的干预效果，同时减少内脏脂肪、保留肌肉量并改善功能 83。
3.3 行为与环境调整
除了饮食和运动干预，行为和环境因素，特别是睡眠质量和压力管理，对内脏脂肪的代谢具有深远影响。优化这些因素是减控内脏脂肪不可或缺的一部分。
3.3.1 睡眠质量与昼夜节律紊乱
睡眠是维持身体各项生理功能正常运作的关键。睡眠不足或昼夜节律紊乱已被证实与内脏脂肪的积累密切相关。
睡眠时长与内脏脂肪： 多项研究表明，睡眠时长与内脏脂肪量之间存在显著关联。一项使用孟德尔随机化分析的研究发现，基因预测的睡眠时长与内脏脂肪（VAT）呈非线性负相关，短睡眠时长是增加内脏脂肪的风险因素。研究显示，基因预测睡眠时长每增加1小时，内脏脂肪量减少0.11公斤（男性减少0.17公斤，女性减少0.07公斤）85。另一项针对中国成年人的队列研究也发现，每晚睡眠时间少于7小时的男性患内脏肥胖的风险显著增加，且睡眠时间越短，风险越高。然而，过长的睡眠时间（超过9小时）也可能与内脏脂肪的增加相关，这提示存在一个“U”型关联，即过短或过长的睡眠都可能带来不利影响。
昼夜节律紊乱的影响： 人体内部存在一个复杂的生物钟系统，即昼夜节律，调控着新陈代谢、激素分泌和睡眠-觉醒周期。昼夜节律紊乱（Chronodisruption），如夜班工作、不规律的作息或睡眠障碍，会扰乱正常的代谢过程，从而促进内脏脂肪的堆积。研究表明，晚睡型（evening chronotypes）个体即使在代谢参数相似的情况下，也表现出更高的内脏脂肪组织炎症水平和改变的生物钟基因表达，可能增加其代谢风险86。此外，有研究指出，习惯性午睡（nappers）的人群在腹部脂肪组织中显示出脂酶E（HSL）基因表达的昼夜节律失调，HSL是脂肪分解的关键酶，其活性下降可能导致腹部脂肪积累87。动物实验也发现，身体不活动与不吃早餐（一种昼夜节律紊乱）协同作用，导致大鼠内脏脂肪显著积累88。
改善睡眠质量的方法： 为了减少内脏脂肪，建议成年人保持7-9小时的规律睡眠。改善睡眠质量的策略包括：
- 建立规律的作息时间： 每天在固定时间睡觉和起床，包括周末。
- 优化睡眠环境： 保持卧室黑暗、安静、凉爽。
- 睡前放松： 避免睡前使用电子产品、摄入咖啡因和酒精，可以进行睡前冥想或听舒缓音乐。
- 午睡： 虽然习惯性午睡与昼夜节律失调相关，但适度的、短时间的午睡（如20-30分钟）对于补充精力、改善认知功能可能是有益的，关键在于避免影响夜间睡眠的长时间或不规律午睡。
3.3.2 压力管理与皮质醇水平调控
慢性压力会导致皮质醇（Cortisol）水平升高，而皮质醇被认为是促进内脏脂肪堆积的重要激素。
皮质醇与内脏脂肪： 皮质醇是一种糖皮质激素，在应激反应中发挥关键作用。长期或反复的应激会导致皮质醇持续高水平分泌，这与内脏脂肪的优先沉积密切相关。研究发现，抑郁症女性的内脏脂肪量和肾上腺体积均增加，且Beck抑郁量表（BDI）评分与上腹部内脏脂肪量呈正相关89。心理压力和皮质醇分泌升高会促进腹部脂肪积累90。儿童时期头发皮质醇浓度（HCC）较高与10岁时更高的肝脂肪分数和非酒精性脂肪肝病（NAFLD）风险相关，尽管与内脏脂肪指数无直接关联91。
应激与饮食的交互作用： 皮质醇与饮食中的糖分摄入之间存在协同作用。一项针对青少年肥胖者的研究发现，在高糖摄入量下，皮质醇水平与内脏脂肪量显著相关，而在低糖摄入量下则无此关联92。这表明，在高压环境下，控制糖分摄入对于预防内脏脂肪堆积尤为重要。
压力管理策略： 有效的压力管理可以帮助降低皮质醇水平，从而有助于减少内脏脂肪：
通过综合改善睡眠质量和有效管理压力，可以辅助减控内脏脂肪，并对整体代谢健康产生积极影响。一些新兴疗法也显示出潜力，例如，一种名为Pep19的新型口服肽在临床试验中发现，可以显著减少内脏脂肪（5mg组减少17±4.7%）并改善睡眠质量（2mg组改善35±10%，5mg组改善25±16%），这可能为未来的干预提供新的方向93。
4. 药物与新型疗法的临床应用
尽管生活方式干预是减控内脏脂肪的基础，但对于部分患者而言，药物和新型疗法提供了更强效或有针对性的治疗选择，尤其是在生活方式干预效果不佳或合并其他代谢性疾病的情况下。
4.1 GLP-1受体激动剂的作用
胰高糖素样肽-1（GLP-1）受体激动剂（GLP-1RAs）是一类新型的降糖药物，最初用于治疗2型糖尿病，但因其显著的减重和心血管保护作用，其应用范围逐渐扩展到肥胖症和代谢综合征的治疗。GLP-1RAs通过多靶点机制有效减少内脏脂肪，并改善整体代谢健康。
4.1.1 GLP-1受体激动剂减少内脏脂肪的临床效果
多项临床研究和Meta分析证实，GLP-1RAs能显著减少内脏脂肪（VAT）和异位脂肪，无论患者是否合并2型糖尿病 9495。
- 利拉鲁肽 (Liraglutide)： 利拉鲁肽是一种广泛研究的GLP-1RA，被证实能有效减少内脏脂肪。一项系统评价和Meta分析纳入16项随机临床试验（共845名受试者）发现，利拉鲁肽能显著降低内脏脂肪（标准均数差 [SMD] = -0.72，95% CI [-1.12, -0.33]）和肝脏脂肪（SMD = -0.78，95% CI [-1.24, -0.32]），同时降低体重指数（加权均数差 = -1.44，95% CI [-1.95, -0.92]）。这种效果不受2型糖尿病状态的影响。亚组分析显示，充足的剂量（≥1.8 mg/天）和适当的治疗持续时间（16至40周）是利拉鲁肽有效减少内脏脂肪的关键因素 94。另一项系统性综述指出，利拉鲁肽可使内脏脂肪体积减少12.49%至23%，凸显了其在靶向内脏脂肪方面的有效性 96。此外，利拉鲁肽也被证实能改善非酒精性脂肪性肝病（NAFLD）患者的胰岛素抵抗，并减少内脏脂肪 9798。
- 替尔泊肽 (Tirzepatide)： 替尔泊肽是一种双重GIP/GLP-1受体激动剂，在减重方面表现出更强的效果。SURMOUNT-1临床试验显示，替尔泊肽在72周内可使体重平均减少15.0%至20.9% 99。虽然该研究未直接报告内脏脂肪的具体减少数据，但其显著的总体减重效果通常伴随着内脏脂肪的减少。另一项比较替尔泊肽与司美格鲁肽（Semaglutide，另一种GLP-1RA）治疗肥胖症的临床试验显示，替尔泊肽在72周时可使体重平均减少20.2%，而司美格鲁肽为13.7%，替尔泊肽在减少腰围方面也优于司美格鲁肽（-18.4 cm vs -13.0 cm），这间接说明了其对腹部脂肪（包括内脏脂肪）的更强效作用 100。一项真实世界的回顾性队列研究也得出相似结论，替尔泊肽在实现≥5%、≥10%和≥15%体重减轻的患者比例上显著高于司美格鲁肽，且在3、6、12个月的平均体重变化更大 101。
- 司美格鲁肽 (Semaglutide)： 司美格鲁肽也展现出显著的减重和内脏脂肪减少潜力。虽然在与替尔泊肽的直接比较中可能效果略逊一筹 100，但其对体重和代谢指标的改善仍非常显著。一项系统评价和网络Meta分析指出，包括司美格鲁肽在内的GLP-1RAs在2型糖尿病患者中显著改善体重管理，其中替尔泊肽和一种司美格鲁肽与cagrilintide的联合制剂CagriSema在减重效果上名列前茅 102。
- 贝那鲁肽 (Beinaglutide)： 作为一种GLP-1RA，贝那鲁肽在肥胖症患者中也显示出积极作用。一项研究发现，贝那鲁肽能显著减少内脏脂肪面积，改善糖脂代谢，并降低总胆固醇、低密度脂蛋白胆固醇、血糖和C反应蛋白水平 103。
4.1.2 GLP-1受体激动剂的多靶点机制
GLP-1RAs减少内脏脂肪的机制是多方面的：
- 抑制食欲与增加饱腹感： GLP-1RAs作用于中枢神经系统的GLP-1受体，特别是下丘脑，通过抑制食欲和增加饱腹感来减少能量摄入，从而导致体重减轻和脂肪消耗 104。
- 延迟胃排空： GLP-1RAs可以延缓胃排空，这有助于延长食物在胃中的停留时间，进一步增强饱腹感，减少餐后血糖波动 104。
- 提高胰岛素敏感性： GLP-1RAs能够促进胰岛素的葡萄糖依赖性分泌，并抑制胰高糖素分泌，从而改善血糖控制。长期使用可改善外周组织和肝脏的胰岛素敏感性，减少胰岛素抵抗，进而降低内脏脂肪的形成和堆积 104105106。例如，GLP-1RAs可以增加胰岛素依赖性组织中葡萄糖转运蛋白的表达，降低炎症反应，减少氧化应激，并调节脂质代谢，这些都有助于改善胰岛素抵抗 105。
- 直接作用于脂肪组织： GLP-1受体在脂肪组织中也有表达，GLP-1RAs可能直接影响脂肪细胞的代谢，促进脂肪分解，减少脂肪生成。研究发现，GLP-1RAs诱导的体重减轻主要反映了腹部内脏脂肪的损失 104。
- 抗炎作用： GLP-1RAs被发现具有抗炎作用，能够减少慢性低度炎症，这对于改善与内脏脂肪相关的代谢紊乱至关重要 105。
- 改善肝脏脂肪： GLP-1RAs可显著减少肝脏脂肪含量，这对于NAFLD患者尤为重要。通过减少肝脏脂肪，可以进一步改善肝脏的代谢功能，降低肝脏对门静脉系统传递的游离脂肪酸的负面响应 95。
值得注意的是，尽管GLP-1RAs在减少内脏脂肪和改善代谢方面表现出显著优势，但其常见的副作用主要是胃肠道反应，如恶心、呕吐、腹泻等，通常为轻中度，并主要发生在剂量递增期间 9499100107。在一些情况下，药物可能导致胃肠道不良事件，尤其是大剂量使用时需关注安全性问题 102。
4.2 传统中药与天然成分干预
在减控内脏脂肪的策略中，传统中药和天然成分因其多靶点作用和较低的副作用受到越来越多的关注。这些天然疗法通过调节炎症通路、改善脂质代谢、促进脂肪细胞分化或褐变等多种机制来发挥作用。
4.2.1 中药复方对内脏脂肪的调节
中药复方通常包含多种活性成分，通过协同作用实现对复杂病症的干预。
姜浊合剂： 姜浊合剂（GGEx）是由多种草药组成的传统韩方，在韩国诊所中被用作抗肥胖药物。动物实验研究表明，姜浊合剂能显著降低OLETF大鼠的食物摄入量、血浆瘦素水平、体重增加和腹部脂肪（包括内脏脂肪）108。此外，姜浊合剂还能降低循环甘油三酯水平，并抑制肝脏脂肪堆积。其作用机制可能与激活肝脏过氧化物酶体增殖物激活受体α（PPARα）靶基因的mRNA水平有关，这些基因负责脂肪酸的β-氧化，从而促进脂肪分解108。在体外实验中，姜浊合剂也能提高NMu2Li肝细胞中PPARα报告基因的表达，进一步证实了其通过PPARα途径干预脂质代谢的能力108。
复方珍珠降脂颗粒（FTZ）： 复方珍珠降脂颗粒是另一种中药复方，被研究发现能有效减少内脏脂肪。研究表明，FTZ可能通过调节TLR4/NF-κB炎症通路来抑制炎症反应，从而改善内脏脂肪堆积。此外，FTZ还能促进白色脂肪的褐变（即白色脂肪转化为具有产热功能的米色脂肪），通过上调UCP1（解偶联蛋白1）和PRDM16（PR结构域包含蛋白16）的表达来实现，这些蛋白是脂肪褐变的关键标志物。白色脂肪褐变能增加能量消耗，从而有助于减少脂肪堆积。
Arq Zeera： Arq Zeera是一种由多种草药提取物制成的蒸馏产品，包括孜然（Trachyspermum ammi L.）、生姜（Zingiber officinale Roxb.）、葛缕子（Carum carvi L.）和小茴香（Cuminum cyminum L.）109。研究发现，Arq Zeera及其主要成分百里香酚和小茴香醛在高脂饮食诱导的肥胖大鼠模型中表现出显著的抗肥胖效果。与对照组相比，Arq Zeera处理组大鼠的体重、食物摄入量、肝脏重量和内脏脂肪垫重量均显著降低109。同时，它还能改善血脂水平（降低甘油三酯、总胆固醇、低密度脂蛋白胆固醇），降低血糖、胰岛素和瘦素水平，并抑制胰脂肪酶活性，从而减少脂肪吸收109。这些结果表明，Arq Zeera通过多种途径发挥降脂、降糖和抗肥胖作用，且其效果可能优于奥利司他（一种常用的减肥药物）109。
4.2.2 天然成分的干预作用
多种天然成分也被证实具有减少内脏脂肪的潜力，它们通常通过改善脂质代谢、抗氧化和抗炎等机制发挥作用。
柿叶提取物（Diospyros lotus leaf extract）： 柿叶中含有丰富的抗氧化和抗炎成分。研究表明，柿叶水提取物（DLE）能有效抑制3T3-L1脂肪细胞的脂质积累和甘油三酯含量110。在高脂饮食诱导的肥胖小鼠模型中，口服DLE能显著降低体重增加、食物效率比、肝脏和内脏脂肪重量110。此外，DLE还能降低血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、血糖、胰岛素和瘦素水平，并改善肝脏脂肪变性和肝酶指标。其抗肥胖机制还包括预防脂质过氧化、恢复谷胱甘肽水平以及提高超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性，表明其具有强大的抗氧化作用110。
酚类化合物： 酚类化合物广泛存在于水果、蔬菜和草药中，因其抗氧化和抗炎特性而备受关注。最近的研究表明，酚类化合物在减少皮下和内脏脂肪沉积方面发挥着重要作用111。通过调节脂质代谢相关基因表达、抑制脂肪细胞分化、促进脂肪分解以及改善胰岛素敏感性，酚类化合物能够有效干预脂肪堆积过程。例如，一些酚类化合物可以激活PPARα，促进脂肪酸氧化，而另一些则可能通过抑制脂肪细胞因子释放来减轻炎症。
荷叶、山楂等： 荷叶和山楂是传统中医药中常用的降脂减肥药材。荷叶中的生物碱和黄酮类物质被认为具有抑制脂肪吸收、促进脂肪分解和降低血脂的作用。山楂则富含黄酮类、有机酸和三萜类化合物，能够促进消化、降低血脂、改善心血管功能。虽然针对其直接减少内脏脂肪的特定机制研究不如复方深入，但其综合的代谢改善作用可能有助于间接减少内脏脂肪的堆积。
4.2.3 血管紧张素II（ANG II）的调控： 血管紧张素II（ANG II）是肾素-血管紧张素系统（RAS）的生物活性成分，在脂肪组织中发挥重要作用。ANG II可以促进脂肪细胞生长和分化，增加脂肪酸和甘油三酯的合成、摄取和储存，并可能抑制脂肪分解112。多项研究表明，阻断ANG II的产生和/或作用，无论是通过药物还是天然物质，都能减少体内脂肪，且这种减少主要发生在腹部脂肪库，且似乎独立于能量摄入和消化率112。因此，一些天然成分可能通过调节RAS系统来影响内脏脂肪的堆积。
总而言之，传统中药复方和天然成分为内脏脂肪的减控提供了丰富的选择。它们通常通过多靶点、多途径的机制来改善脂质代谢、炎症反应和能量消耗，从而达到减少内脏脂肪、改善代谢健康的目的。然而，仍需要更多高质量的临床研究来进一步验证其有效性和安全性，并阐明其精确的作用机制。
4.3 益生菌与肠道微生态调节
肠道微生物群在宿主能量代谢和脂肪分布中扮演着至关重要的角色。益生菌作为调节肠道微生态的重要手段，通过多种机制影响内脏脂肪的堆积。
4.3.1 益生菌抑制内脏脂肪堆积的机制
益生菌主要通过以下途径干预内脏脂肪：
- 改善肠道屏障功能： 肠道菌群失调和高脂饮食可导致肠道通透性增加，使得细菌内毒素（如脂多糖, LPS）进入血液循环，引发全身性炎症反应，进而促进内脏脂肪堆积和胰岛素抵抗。益生菌，特别是乳酸杆菌和双歧杆菌属，能够增强肠道上皮细胞的紧密连接，修复受损的肠道屏障，减少LPS的跨膜转运，从而降低炎症反应，抑制内脏脂肪的异常积累。例如，丁酸及其甘油三酯形式可以显著减少脂多糖（LPS）诱导的人体内脏脂肪组织炎症细胞因子和趋化因子的产生。
- 增加短链脂肪酸（SCFAs）生成： 益生菌能够发酵膳食纤维产生短链脂肪酸（如丁酸、丙酸、乙酸）。SCFAs是肠道细胞的能量来源，同时具有多种代谢调节功能。丁酸被发现可以增加内脏脂肪中的ST2调节性T细胞数量，改善葡萄糖耐受和内脏炎症。SCFAs还可以通过激活肠道L细胞分泌GLP-1和肽YY（PYY），调节食欲和能量平衡，从而间接减少内脏脂肪。此外，SCFAs可能通过调节肝脏和脂肪组织中的脂质代谢，抑制脂肪生成。
- 调节宿主能量代谢： 益生菌可以通过影响肝脏和脂肪组织的脂质代谢、胰岛素敏感性以及食欲调节激素来干预内脏脂肪。例如，一些益生菌能够减少肝脏脂肪合成，增加脂肪酸氧化，从而降低肝脏和内脏的脂肪含量。它们还可以改善胰岛素信号传导，提高胰岛素敏感性。
- 抗炎作用： 许多益生菌菌株具有直接的抗炎作用，通过调节免疫细胞功能和细胞因子分泌，减轻由内脏脂肪引起的慢性低度炎症。这有助于打破炎症-胰岛素抵抗-脂肪堆积的恶性循环。
- 影响胆汁酸代谢： 肠道菌群参与胆汁酸的代谢，而胆汁酸不仅有助于脂肪消化吸收，还作为信号分子调节糖脂代谢。益生菌可以通过改变胆汁酸谱，影响其对肠道菌群和宿主代谢的调节作用。
4.3.2 益生菌对腰围及VAT的干预效果
多项临床研究和Meta分析评估了益生菌补充剂对肥胖相关指标，包括内脏脂肪的干预效果。
- 一项系统评价和Meta分析发现，益生菌补充剂在超重和肥胖人群中能显著减少腰围和体脂率，但对体重和BMI的干预效果不显著。这表明益生菌可能对腹部脂肪（包括内脏脂肪）有更特异性的作用。
- 乳酸双歧杆菌（Bifidobacterium lactis）是研究较多的益生菌之一。一项双盲、安慰剂对照研究发现，在成年肥胖受试者中，补充乳酸双歧杆菌V9能显著降低体重、腰围、臀围、BMI以及内脏脂肪面积，改善血清空腹胰岛素、胰岛素抵抗指数（HOMA-IR）和甘油三酯水平，并增加高密度脂蛋白胆固醇。
- 另一项Meta分析纳入了7项随机对照试验（共306名受试者），旨在评估益生菌对内脏脂肪的影响。结果显示，益生菌补充剂可以显著降低超重/肥胖成年人的内脏脂肪面积（SMD = -0.37，95% CI [-0.60, -0.15]）。亚组分析显示，干预时间大于12周的益生菌补充剂效果更显著。
- 益生元（如低聚果糖）与益生菌的联合使用（合生元）也被发现能更有效地改善肠道菌群，降低体重、BMI和内脏脂肪。
- 一些研究还指出，特定的益生菌菌株组合，如含有乳酸菌和双歧杆菌的混合制剂，在改善代谢综合征患者的内脏脂肪和血脂方面表现出更优异的效果。
尽管研究结果令人鼓舞，但益生菌的种类、剂量、干预时间以及个体肠道菌群的差异都可能影响其效果。未来需要更多的个性化研究来明确不同益生菌制剂在不同人群中减控内脏脂肪的最佳方案。
5. 特殊人群的针对性减控策略
内脏脂肪的减控策略需要根据个体的年龄、性别、健康状况等特殊性进行调整，以实现更精准、高效的干预。
5.1 绝经后女性的综合管理
绝经后女性由于雌激素水平下降，内脏脂肪堆积风险显著增加，同时伴随骨质疏松和肌肉量流失的风险。因此，针对这一群体的内脏脂肪管理需要综合考虑激素替代治疗和生活方式干预。
5.1.1 雌激素替代治疗（ERT）与内脏脂肪
绝经后雌激素水平的下降是导致脂肪重新分布，内脏脂肪优先堆积的关键因素。因此，雌激素替代治疗（Estrogen Replacement Therapy, ERT）被认为是逆转或减缓这一过程的潜在策略。
- ERT对脂肪分布的影响： ERT可以通过补充雌激素，部分恢复绝经前雌激素对脂肪分布的调节作用，从而减少内脏脂肪的堆积，并增加或维持皮下脂肪。研究表明，口服激素替代疗法（HT）可以显著提高绝经后女性皮下和内脏脂肪中的雌酮和雌二醇浓度，并降低内脏脂肪中的睾酮水平，从而提高局部雌激素与雄激素的比率，这可能有助于预防与绝经相关的腹部肥胖。
- ERT的局限性与风险： 尽管ERT在改善脂肪分布方面具有潜在益处，但其长期使用的风险，如增加乳腺癌和心血管疾病的风险，使其应用受到限制。对于老年绝经后女性，雌激素补充剂可能通过靶向IGF2BP1恶化内脏脂肪功能，导致促炎细胞因子增加和胰岛素敏感性降低，这提示在选择ERT时需要权衡利弊并进行个体化评估。
5.1.2 生活方式干预的协同作用
无论是否采用ERT，生活方式干预始终是绝经后女性减控内脏脂肪的核心。将其与ERT结合使用，可以产生协同效应。
- 饮食调整： 建议采用低热量、均衡营养的饮食模式，如地中海饮食。地中海饮食富含植物性食物、全谷物和不饱和脂肪酸，有助于减少炎症，改善脂质代谢，并降低心血管疾病风险。一项研究表明，基于地中海饮食的限能量饮食（能量减少）结合体力活动，能显著减少超重或肥胖且伴有代谢综合征的中老年人的总脂肪和内脏脂肪储存。
- 运动干预： 针对绝经后女性，推荐采用有氧运动与抗阻训练相结合的组合运动方案：
- 有氧运动： 旨在提高能量消耗，减少内脏脂肪。如快走、慢跑、游泳等，每周至少150分钟中等强度有氧运动。
- 抗阻训练： 绝经后女性面临肌肉量流失的风险，抗阻训练能有效维持或增加肌肉量，提高基础代谢率，从而有助于脂肪消耗。研究表明，在老年肥胖人群中，组合运动（有氧+抗阻）相比单一运动模式，能更显著地减少内脏脂肪和肌间脂肪，并改善胰岛素敏感性。
- 骨骼健康： 结合抗阻训练还能刺激骨骼生长，对抗绝经后骨质疏松。
- 综合方案： 理想的综合管理方案可能包括在医生指导下，对适宜的患者短期或低剂量使用ERT以改善脂肪分布和骨骼健康，同时长期坚持低热量、均衡的饮食，并结合有氧与抗阻训练，以最大限度地减少内脏脂肪，并改善整体代谢健康和生活质量。
5.2 老年肥胖者的功能保护
老年肥胖者常伴有肌少症（肌肉量减少）和内脏脂肪增加，形成肌少性肥胖，这不仅增加跌倒、失能的风险，也加剧代谢紊乱。因此，在减控内脏脂肪的同时，保护和增加肌肉量是老年肥胖者干预策略的关键目标。
5.2.1 预防肌少性肥胖及相关功能衰退的重要性
肌少性肥胖对老年人的健康危害极大：
- 代谢风险增加： 肌肉是重要的葡萄糖消耗器官，肌肉量减少会进一步加剧胰岛素抵抗，使血糖更难控制。内脏脂肪的炎症效应也加重代谢紊乱。
- 身体功能下降： 肌肉力量和质量的下降直接导致活动能力减退，影响日常生活自理能力，增加跌倒和骨折的风险。
- 死亡率升高： 肌少性肥胖被认为是独立预测老年人全因死亡率和心血管死亡率的风险因素。
因此，老年肥胖者的干预目标不仅是“减重”，更是“减脂增肌”，改善身体成分和功能状态。
5.2.2 推荐组合运动（有氧+抗阻）联合优质蛋白饮食
- 组合运动的优势： 如前所述，有氧运动（如快走、慢跑）能有效燃烧脂肪，特别是内脏脂肪，改善心肺功能。抗阻训练（如举重、使用弹力带）则能刺激肌肉合成，增加肌肉量和力量。将两者结合的组合运动，在老年肥胖人群中表现出最佳效果。一项针对老年肥胖者的随机对照试验显示，组合运动相比单一的有氧或抗阻训练，能更显著地减少内脏脂肪（VAT减少36%）、肌间脂肪（IMAT减少41%），同时改善胰岛素敏感性、体力功能和肌肉力量。这种综合效应有助于同时解决内脏脂肪过量和肌肉量不足的问题。
- 优质蛋白饮食： 老年人常因食欲下降、消化吸收能力减弱等原因导致蛋白质摄入不足，加速肌肉流失。因此，在减控总热量的同时，保证充足的优质蛋白质摄入至关重要。
- 蛋白质摄入量： 推荐老年人每日蛋白质摄入量达到1.0-1.2克/公斤体重，甚至更高（如1.2-1.5克/公斤体重），以支持肌肉合成，尤其是在进行抗阻训练期间。
- 蛋白质来源： 优先选择富含亮氨酸（Leucine）的优质蛋白质来源，如乳制品（牛奶、酸奶、奶酪）、瘦肉、鱼类、鸡蛋和豆制品。亮氨酸是刺激肌肉蛋白质合成的关键氨基酸。
- 摄入时间： 将蛋白质摄入均匀分配到一日三餐，并在运动后30-60分钟内摄入蛋白质，以最大化肌肉修复和生长的效果。
- 其他营养素： 补充维生素D和钙也有助于维持骨骼和肌肉健康。
综上，针对老年肥胖者，减控内脏脂肪应以“功能保护”为核心，通过“组合运动+优质蛋白饮食”的协同干预，在减少内脏脂肪的同时，最大限度地保留甚至增加肌肉量，从而改善整体身体功能，提高生活质量，并预防相关的代谢性疾病和不良健康结局。
5.3 代谢综合征患者的多靶点干预
代谢综合征是一组相互关联的代谢紊乱，主要表现为腹部肥胖（内脏脂肪堆积）、高血糖、高血压和血脂异常。内脏脂肪的过量堆积是代谢综合征的核心驱动因素，其减少对改善所有代谢指标至关重要 113。对于已确诊代谢综合征的患者，单一的生活方式干预往往不足以有效管理，因此需要采用药物与生活方式干预相结合的多靶点综合方案。
5.3.1 GLP-1受体激动剂在代谢综合征中的应用
GLP-1受体激动剂（GLP-1RAs）已被证明在改善代谢综合征的多个方面具有显著优势，特别是在减少内脏脂肪和改善血糖控制方面。
- 对内脏脂肪的特异性减少： 临床研究证实，利拉鲁肽等GLP-1RAs能显著减少内脏脂肪（VAT）和肝脏脂肪，即使在未伴有2型糖尿病的超重或肥胖个体中也有效 114115。例如，在PCOS女性中，利拉鲁肽治疗26周可使内脏脂肪减少18%，肝脏脂肪含量减少44%，同时降低HbA1c、空腹血糖和瘦素水平 114。另一项针对心血管高风险超重或肥胖成年人的研究显示，利拉鲁肽3.0 mg联合生活方式干预可使内脏脂肪平均减少12.49% 115。这种内脏脂肪的减少被认为是GLP-1RA改善心血管结局的重要机制之一 115116。
- 改善血糖和胰岛素敏感性： GLP-1RAs通过促进胰岛素葡萄糖依赖性分泌、抑制胰高血糖素分泌、延缓胃排空和抑制食欲，从而有效降低血糖和改善胰岛素抵抗 116。这对于合并高血糖的代谢综合征患者至关重要。
- 心血管保护作用： 除了对代谢指标的改善，GLP-1RAs还具有独立的心血管保护作用，包括降低血压、改善血脂、减轻炎症和氧化应激，这些都进一步支持其在代谢综合征患者中的应用 116。
5.3.2 联合饮食-运动的生活方式干预
药物治疗应始终与积极的生活方式干预相结合，以达到最佳的治疗效果和长期维持。
饮食优化方案：
- 低热量饮食： 能量限制是减少内脏脂肪和改善代谢综合征的基础 117。无论采用何种饮食模式，确保总能量摄入低于消耗是减重和减脂的前提。
- 地中海饮食或抗炎饮食： 针对代谢综合征患者，推荐采纳地中海饮食或具有抗炎特性的饮食模式。这些饮食富含膳食纤维、不饱和脂肪酸和抗氧化剂，有助于减少炎症、改善胰岛素敏感性、调节血脂和血压 117。一项研究显示，抗炎饮食干预24周能显著减少体重和内脏脂肪，并改善心血管代谢和炎症状态 117。
- 低碳水化合物/低糖饮食： 限制精制碳水化合物和添加糖的摄入，特别是果糖，可以显著减少肝脏脂肪生成和内脏脂肪堆积，改善胰岛素抵抗 118。
- 高蛋白饮食： 在能量限制的同时，保持足够的蛋白质摄入有助于维持肌肉量，避免肌少症。一项针对肥胖患者的研究发现，在多学科团队的管理下，高蛋白饮食组与标准蛋白饮食组在体重减轻、内脏脂肪面积减少和瘦体重维持方面没有统计学上的显著差异 119。
运动干预：
5.3.3 VAT减少与代谢指标改善的相关性
内脏脂肪的减少与代谢综合征患者多个代谢指标的改善密切相关：
- 胰岛素敏感性： 内脏脂肪的减少直接降低了进入肝脏的游离脂肪酸负荷，减轻肝脏胰岛素抵抗，从而改善全身胰岛素敏感性 113121。一项研究发现，仅通过生活方式干预实现5%的体重减轻，就能在12年随访期内将2型糖尿病风险降低80%，这主要归因于内脏脂肪和肝脏脂肪的显著减少以及胰岛素敏感性的提升 120。
- 血脂异常： 内脏脂肪减少有助于降低甘油三酯水平，改善低密度脂蛋白胆固醇（LDL-c）的颗粒大小和密度，从而降低动脉粥样硬化风险。一项多学科团队对肥胖患者进行管理的研究表明，在体重减轻的同时，HDL-c水平也随之升高 119。
- 血压： 减肥药物可以通过改善心血管风险因素如高血压、高脂血症和胰岛素抵抗来发挥作用 116。
- 非酒精性脂肪性肝病（NAFLD）： 由于内脏脂肪与肝脏脂肪存在直接关联，内脏脂肪的减少是改善NAFLD的关键。多项研究显示，GLP-1RAs和生活方式干预均能显著减少肝脏脂肪含量 114120122。
综上所述，对于代谢综合征患者，采用GLP-1RAs等药物联合个性化的饮食和运动干预，能够实现内脏脂肪的有效减少，进而全面改善高血糖、高血压、血脂异常等代谢紊乱，并最终降低心血管疾病的风险。这种多靶点、综合性的治疗策略是提高患者预后的关键。
6. 减控效果评估与长期维持
有效的内脏脂肪减控不仅需要科学的干预策略，更离不开准确的评估方法和长期的维持机制。对减控效果的评估有助于及时调整策略，而对维持要素的理解则能帮助个体避免反弹，实现长期的健康目标。
6.1 内脏脂肪的评估方法
准确评估内脏脂肪（VAT）的含量对于指导临床干预和监测治疗效果至关重要。目前，评估内脏脂肪的方法多样，从简便的体格测量到精准的影像学技术，各有优缺点。
6.1.1 常用评估手段及其优缺点
腰围 (Waist Circumference, WC)：
体重指数 (Body Mass Index, BMI)：
磁共振成像 (Magnetic Resonance Imaging, MRI)：
计算机断层扫描 (Computed Tomography, CT)：
双能X射线吸收法 (Dual-energy X-ray Absorptiometry, DXA)：
生物电阻抗分析 (Bioelectrical Impedance Analysis, BIA)：
矢状腹径 (Sagittal Abdominal Diameter, SAD)：
6.1.2 推荐的动态评估体系
鉴于各种评估方法的优缺点，建议采用临床与自我监测相结合的动态评估体系：
家庭自我监测：
- 定期腰围测量： 作为最简便的自我监测方法，每月或每两周固定时间测量腰围，可以初步判断腹部脂肪的趋势变化。建议使用“腰围观察尺”（Waist Watcher）等工具，可提高测量准确性并进行风险自评 124。
- 体重与BMI监测： 每日或每周监测体重，结合身高计算BMI，以追踪整体体重变化。
- 矢状腹径（SAD）测量： 如果条件允许，在家中定期测量SAD，作为更精确反映内脏脂肪变化的指标。
临床专业评估：
- 影像学检查： 对于初步评估为高风险、或需要精确了解内脏脂肪含量及分布、或评估干预效果的患者，建议定期进行MRI或CT检查（每年或每半年一次，根据风险程度和医生建议）。MRI因无辐射更适合多次复查。
- BIA身体成分分析： 作为一种补充手段，BIA可提供体脂率、肌肉量等整体身体成分信息，帮助综合评估减控效果。
- 血生化指标： 定期检测血糖、血脂、肝功能、胰岛素抵抗指数等代谢指标，以综合判断内脏脂肪减少对代谢健康的影响。
通过结合上述方法，可以形成一个全面、动态的内脏脂肪评估体系，既能方便地进行日常监测，又能获得专业、精确的诊断数据，从而确保减控策略的有效性和安全性。
6.2 长期维持的关键要素
成功减控内脏脂肪仅仅是第一步，更具挑战性的是如何防止其反弹并实现长期健康的维持。这需要多方面的策略，包括固化行为习惯、建立社会支持系统以及根据身体适应性进行阶段性调整。
6.2.1 行为习惯的固化
良好的行为习惯是长期维持内脏脂肪减控效果的基石。
- 饮食记录与自我监测： 持续的饮食记录（如食物日记或使用手机APP）能帮助个体更好地了解自己的饮食模式和能量摄入，及时发现并纠正不健康的饮食行为。这种自我监测行为已被证明与长期体重维持呈正相关。记录不仅限于食物种类和份量，还可以包括进食时间、情绪状态等，从而识别潜在的饮食触发因素。
- 运动依从性： 将运动融入日常生活是至关重要的。这意味着选择自己喜欢并能长期坚持的运动形式，并制定切实可行的运动计划。研究表明，有氧运动与体重减轻和内脏脂肪减少相关，尽管其对体重维持的直接证据尚不完全确凿，但较高的运动量对于体重维持具有价值 132。定期评估运动强度和类型，并根据身体状况进行调整，有助于保持运动兴趣和依从性。例如，可以尝试不同的运动项目，或与朋友一起运动，增加乐趣和社交性。
- 其他健康行为的养成： 除了饮食和运动，充足的睡眠、压力管理（如通过正念冥想）和戒烟限酒等健康行为也应成为日常生活的一部分。这些行为有助于维持内分泌平衡，减少炎症反应，从而间接支持内脏脂肪的长期管理。
6.2.2 社会支持与环境调整
社会支持和积极的环境因素在长期减控内脏脂肪中发挥着不可替代的作用。
- 家庭监督与参与： 家庭成员的支持和理解对个体维持健康生活方式至关重要。家庭监督可以包括共同制定健康饮食计划、一起参与体育活动、互相鼓励等。研究显示，配偶或家庭成员的积极参与能够显著提高减肥成功的概率。一项荟萃分析发现，基于社会支持的减重干预在干预结束时及3-6个月随访时显示出显著效果 133。
- 社区健康管理与同伴支持： 参与社区健康项目、减肥支持小组或拥有志同道合的同伴，可以提供情感支持、信息交流和经验分享，增强个体的归属感和坚持下去的动力。例如，减肥手术后的患者对术后营养建议的高依从性与更少的蛋白质和矿物质流失、以及最大化的内脏脂肪减少相关 134。护士主导的糖尿病自我管理教育计划可以显著改善患者的糖化血红蛋白、血压、体重和自我管理行为 135。这说明专业的社区管理和指导对长期健康管理的重要性。
- 环境改造： 创造一个支持健康行为的物理环境，例如，家中减少不健康零食的储存、增加新鲜蔬果的可见性；选择步行或骑自行车上班；积极利用公园、健身房等运动设施。
6.2.3 阶段性调整与个体化策略
身体会对长期的减脂过程产生适应性改变，因此需要根据这些变化进行阶段性调整。
- 根据代谢适应性调整运动强度： 随着体重的下降和体能的提高，身体的基础代谢率可能会略有下降，同时运动所消耗的能量也会减少。因此，需要定期评估运动效果，并逐渐增加运动强度、时间或频率，以持续刺激脂肪燃烧。例如，可以从快走转向慢跑，或增加抗阻训练的重量和组数。
- 调整饮食结构以应对平台期： 在减脂过程中，往往会出现“平台期”，即体重和脂肪减少的速度变慢甚至停滞。此时，可能需要重新评估饮食结构，进行微调，例如进一步减少精制碳水化合物摄入，增加蛋白质和膳食纤维，或者尝试短期热量循环，以打破身体的适应性。
- 心理调适与应对挫折： 长期减控过程中难免会遇到挫折或反弹。学习如何识别并应对这些挑战，例如通过寻求专业心理咨询、调整心态、设定实际目标等，对于防止复胖至关重要。研究发现，提升个体自主性支持和自主性自我调节能力，有助于更好的体重减轻效果 136。
- 定期专业评估： 保持与医生或营养师的定期沟通，进行专业的身体成分评估（如使用BIA或DXA监测体脂率、肌肉量和内脏脂肪水平），并根据评估结果和个人健康状况，及时调整干预方案。这有助于确保减控策略的科学性和持续性。
通过上述多方面的努力，将减控内脏脂肪上升为一种可持续的健康生活方式，才能最大限度地降低反弹风险，并实现长期的健康收益 137138。
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10Pathophysiology of ObesityPubMed
Deepesh Khanna, Brian S. Welch, Anis Rehman
Obesity is one of the most common preventable diseases. It is a major public health concern. Obesity has a multifactorial etiology that includes genetic, environmental, socioeconomic, and behavioral or psychological influences. Obesity results from a chronic positive energy balance regulated by a complex interaction between endocrine tissues and the central nervous system. Obesity measurement can also be used to estimate morbidity and mortality. Body mass index (BMI) has been used to screen overweight and obese individuals. However, waist circumference is the best anthropometric indicator of visceral fat and a better predictor of metabolic disorders such as diabetes, hypertension, and dyslipidemia. People with a normal BMI with a large waist are at higher risk. However, combining BMI and waist circumference adds relatively less risk prediction since they are collinear in nature. Furthermore, hip circumference is inversely related to metabolic syndrome. Large hip circumference is related to lower risks of diabetes and coronary heart disease. This is probably due to having a large muscle mass in the hip region. Compared to the Body Mass Index (BMI), the Visceral Adiposity Index (VAI) is a more specific and sensitive examination tool. The VAI is, therefore, a reliable indicator of increased patient risk for cardiometabolic diseases.[7] There is currently a lack of scientific knowledge regarding the biochemical and physiologic mechanisms associated with this. A possible explanation for the increased specificity and sensitivity of the VAI is that visceral fat has direct access to the portal venous system, whereas subcutaneous white adipose tissue does not. Obesity has inflammatory components, directly and indirectly, related to major chronic diseases such as diabetes, atherosclerosis, hypertension, and several types of cancer. Overweight and obese individuals have altered circulatory levels of inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), IL-18, resistin, and visfatin. Measures of body fat have a stronger correlation with inflammatory markers than BMI. Exercise and dietary restrictions have been strongly advocated to reduce weight gain and its related complications. Caloric restriction has been proven effective in reducing inflammation in obesity. However, a few studies showed that dietary weight loss has less impact on a long-term anti-inflammatory intervention. On the other hand, regular exercise significantly affects chronic inflammation related to obesity and obesity-associated conditions such as hypertension, diabetes, dyslipidemia, etc. Obesity and its inflammatory markers have significant effects on hypertension, diabetes, and other chronic conditions. This review provides detailed insight into chronic inflammation and immune and hormonal disturbance related to the pathophysiology of obesity and their effects on chronic conditions.
11Role of bile acids and bile acid receptors in metabolic regulation.PubMed
Philippe Lefebvre, Bertrand Cariou, Fleur Lien, et al.
Physiol Rev. 2009 Jan;89(1):147-91. doi: 10.1152/physrev.00010.2008.
The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be defined as a cluster of cardiovascular disease risk factors including visceral obesity, insulin resistance, dyslipidemia, increased blood pressure, and hypercoagulability. The farnesoid X receptor (FXR) belongs to the superfamily of ligand-activated nuclear receptor transcription factors. FXR is activated by bile acids, and FXR-deficient (FXR(-/-)) mice display elevated serum levels of triglycerides and high-density lipoprotein cholesterol, demonstrating a critical role of FXR in lipid metabolism. In an opposite manner, activation of FXR by bile acids (BAs) or nonsteroidal synthetic FXR agonists lowers plasma triglycerides by a mechanism that may involve the repression of hepatic SREBP-1c expression and/or the modulation of glucose-induced lipogenic genes. A cross-talk between BA and glucose metabolism was recently identified, implicating both FXR-dependent and FXR-independent pathways. The first indication for a potential role of FXR in diabetes came from the observation that hepatic FXR expression is reduced in animal models of diabetes. While FXR(-/-) mice display both impaired glucose tolerance and decreased insulin sensitivity, activation of FXR improves hyperglycemia and dyslipidemia in vivo in diabetic mice. Finally, a recent report also indicates that BA may regulate energy expenditure in a FXR-independent manner in mice, via activation of the G protein-coupled receptor TGR5. Taken together, these findings suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.
12Association of metabolic syndrome and chronic kidney disease.PubMed
Florian G Scurt, Maximilian J Ganz, Carolin Herzog, et al.
Obes Rev. 2024 Jan;25(1):e13649. doi: 10.1111/obr.13649. Epub 2023 Oct 2.
The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.
13Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.PubMed
Andrew D Hildreth, Feiyang Ma, Yung Yu Wong, et al.
Nat Immunol. 2021 May;22(5):639-653. doi: 10.1038/s41590-021-00922-4. Epub 2021 Apr 27.
White adipose tissue (WAT) is an essential regulator of energy storage and systemic metabolic homeostasis. Regulatory networks consisting of immune and structural cells are necessary to maintain WAT metabolism, which can become impaired during obesity in mammals. Using single-cell transcriptomics and flow cytometry, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of healthy lean and obese human WAT. We report new subsets and developmental trajectories of adipose-resident innate lymphoid cells, dendritic cells and monocyte-derived macrophage populations that accumulate in obese WAT. Analysis of cell-cell ligand-receptor interactions and obesity-enriched signaling pathways revealed a switch from immunoregulatory mechanisms in lean WAT to inflammatory networks in obese WAT. These results provide a detailed and unbiased cellular landscape of homeostatic and inflammatory circuits in healthy human WAT.
14A indicator of visceral adipose dysfunction to evaluate metabolic health in adult Chinese.PubMed
Ming-Feng Xia, Ying Chen, Huan-Dong Lin, et al.
Sci Rep. 2016 Dec 1;6:38214. doi: 10.1038/srep38214.
Visceral adipose dysfunction is a major cause of metabolic disorders. However, there is lack of a clinical index for prediction of visceral fat dysfunction in Asians. The present study aims to establish a visceral adiposity index for evaluation of metabolic health status in Chinese, the largest Asian ethnic group. 485 subjects were recruited from Lianqian Community, Xiamen and received abdominal computed tomography(CT) for visceral fat area. A Chinese visceral adiposity index (CVAI) was created using multivariate linear regression analyses, and was further validated in 6495 subjects recruited from Changfeng Community, Shanghai. CVAI was well associated with visceral obesity (r = 0.68, P < 0.001) and HOMA-IR (r = 0.60, P < 0.001). The AUROCs were 0.89(0.88-0.90), 0.72(0.71-0.73), 0.69(0.68-0.71) and 0.67(0.65-0.68) for determination of metabolic syndrome, hypertension, diabetes and prediabetes, respectively. CVAI was more valuable compared to BMI and waist circumference in evaluation of metabolic risks (all P < 0.001), even in subjects with metabolically unhealthy normal weight (MUNW) and metabolically healthy obese/overweight (MHO). This study demonstrates that CVAI is a reliable and applicable index for evaluation of visceral fat dysfunction in Chinese. It might be used to evaluate metabolic health status in Asians.
15Non-alcoholic fatty liver disease and heart failure: A comprehensive bioinformatics and Mendelian randomization analysis.PubMed
Yayun Zhang, Lu Feng, Xin Guan, et al.
ESC Heart Fail. 2024 Dec;11(6):4185-4200. doi: 10.1002/ehf2.15019. Epub 2024 Aug 14.
AIMS: Heart failure (HF) and non-alcoholic fatty liver disease (NAFLD) are significant global health issues with a complex interrelationship. This study investigates their shared biomarkers and causal relationships using bioinformatics and Mendelian randomization (MR) approaches. METHODS: We analysed NAFLD and HF datasets from the Gene Expression Omnibus (GEO). The GSE126848 dataset included 57 liver biopsy samples [14 healthy individuals, 12 obese subjects, 15 NAFL patients and 16 non-alcoholic steatohepatitis (NASH) patients]. The GSE24807 dataset comprised 12 NASH samples and 5 healthy controls. The GSE57338 dataset included 313 cardiac muscle samples [177 HF patients (95 ischaemic heart disease patients and 82 idiopathic dilated cardiomyopathy patients) and 136 healthy controls]. The GSE84796 dataset consisted of 10 end-stage HF patients and 7 healthy hearts procured from organ donors. We identified differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network. Functional pathways were elucidated through enrichment analyses using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneMANIA annotation. Single nucleotide polymorphism (SNP) data for HF and NAFLD were sourced from genome-wide association studies (GWAS). The HF dataset included 486 160 samples (14 262 experimental and 471 898 control), and the NAFLD dataset comprised 377 988 samples (4761 experimental and 373 227 control). MR analysis investigates the causal interrelations. RESULTS: Our analysis revealed 4032 DEGs from GSE126848 and 286 DEGs from GSE57338. The top 10 hub genes (CD163, VSIG4, CXCL10, FCER1G, FPR1, C1QB, CCR1, C1orf162, MRC1 and CD38) were significantly enriched in immune response, calcium ion concentration regulation and positive regulation of monocyte chemotaxis. CIBERSORT analysis indicated associations between these hub genes and natural killer (NK) cells and macrophages. Transcription factor (TF) target prediction for CD38, CXCL10 and CCR1 highlighted related TFs. A two-sample MR analysis confirmed a bidirectional causal relationship between NAFLD and HF. The main method [inverse variance weighted (IVW)] demonstrated a significant positive causal relationship between NAFLD and HF [P = 0.037; odds ratio (OR) = 1.024; 95% confidence interval (CI): 1.001 to 1.048]. Similarly, HF was associated with an increase in the risk of NAFLD (P < 0.001; OR = 1.117; 95% CI: 1.053 to 1.185). CONCLUSIONS: Our findings reveal novel molecular signatures common to NAFLD and HF and confirm their bidirectional causality, highlighting the potential for targeted therapeutic interventions and prompting further investigation into their intricate relationship.
16Interdisciplinary perspectives on the co-management of metabolic dysfunction-associated steatotic liver disease and coronary artery disease.PubMed
Jacob J Gries, Jeffrey V Lazarus, Paul N Brennan, et al.
Lancet Gastroenterol Hepatol. 2025 Jan;10(1):82-94. doi: 10.1016/S2468-1253(24)00310-8.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a public health threat as it affects approximately 38% of the adult population worldwide, with its prevalence rising in step with that of obesity and type 2 diabetes. Beyond the implications of MASLD for liver health, it is also associated with cardiovascular and vascular dysfunction. Although the many shared risk factors and common metabolic milieu might indicate that cardiovascular disease and MASLD are discrete outcomes from common systemic pathogeneses, a growing body of evidence has identified a potential causal relationship between MASLD and coronary artery disease, which is the leading cause of morbidity and mortality in people with MASLD and all-cause mortality worldwide. This Review takes an interdisciplinary approach, drawing on hepatology, cardiology, endocrinology, and metabolic and internal medicine specialists to help to delineate the intricate interplay between MASLD and coronary artery disease. It sheds light on novel opportunities for targeted interventions and personalised management strategies.
17How non-alcoholic fatty liver disease and cirrhosis affect the heart.PubMed
Søren Møller, Signe Wiese, Mads Barløse, et al.
Hepatol Int. 2023 Dec;17(6):1333-1349. doi: 10.1007/s12072-023-10590-1. Epub 2023 Sep 28.
Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field.
18Assessment of Epicardial Fat in Children: Its Role as a Cardiovascular Risk Factor and How It Is Influenced by Lifestyle Habits.PubMed
Valeria Calcaterra, Hellas Cena, Vittoria Garella, et al.
Nutrients. 2024 Jan 31;16(3):420. doi: 10.3390/nu16030420.
Epicardial adipose tissue (EAT) stands out as a distinctive repository of visceral fat, positioned in close anatomical and functional proximity to the heart. EAT has emerged as a distinctive reservoir of visceral fat, intricately interlinked with cardiovascular health, particularly within the domain of cardiovascular diseases (CVDs). The aim of our overview is to highlight the role of EAT as a marker for cardiovascular risk in children. We also explore the influence of unhealthy lifestyle habits as predisposing factors for the deposition of EAT. The literature data accentuate the consequential impact of lifestyle choices on EAT dynamics, with sedentary behavior and unwholesome dietary practices being contributory to a heightened cardiovascular risk. Lifestyle interventions with a multidisciplinary approach are therefore pivotal, involving a nutritionally balanced diet rich in polyunsaturated and monounsaturated fatty acids, regular engagement in aerobic exercise, and psychosocial support to effectively mitigate cardiovascular risks in children. Specific interventions, such as high-intensity intermittent training and circuit training, reveal favorable outcomes in diminishing the EAT volume and enhancing cardiometabolic health. Future clinical studies focusing on EAT in children are crucial for advancing our understanding and developing targeted strategies for cardiovascular risk management in this population.
19Perivascular adipose tissue: An unique fat compartment relevant for the cardiometabolic syndrome.PubMed
D I Siegel-Axel, H U Häring
Rev Endocr Metab Disord. 2016 Mar;17(1):51-60. doi: 10.1007/s11154-016-9346-3.
Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment.
20Interpretable machine learning analysis of immunoinflammatory biomarkers for predicting CHD among NAFLD patients.PubMed
Wenyuan Dong, Hongcheng Jiang, Yu Li, et al.
Cardiovasc Diabetol. 2025 Jul 3;24(1):263. doi: 10.1186/s12933-025-02818-1.
BACKGROUND: Coronary Heart Disease (CHD) and Non-Alcoholic Fatty Liver Disease (NAFLD) share overlapping pathogenic mechanisms including adipose tissue dysfunction, insulin resistance, and systemic inflammation mediated by adipokines. However, the specific impact of inflammation and immune responses on CHD risk in NAFLD patients remains poorly understood. This study evaluated the predictive value of ten immunoinflammatory indexes for CHD risk in NAFLD patients using an interpretable machine learning framework. METHODS: We retrospectively analyzed 407 NAFLD patients undergoing coronary angiography, and stratifying them into NAFLD + CHD (n = 250) and NAFLD (n = 157) groups. Ten immunoinflammatory indexes were derived from the blood laboratory results. Lasso regression analysis and propensity score matching (PSM) were employed to mitigate confounding effects. Subsequently, univariate and multivariate logistic regression analyses were used to identify independent risk factors for CHD occurrence among NAFLD patients. While restricted cubic splines (RCS) and Receiver operating characteristic (ROC) curve evaluated the relationship between each immunoinflammatory indexes and CHD risk. Linear correlation methods were employed to evaluate the relationship between Gensini score and immunoinflammatory indexes. Finally, three machine learning algorithms (RF, SVM and GLM) were used to identify significant risk factors. To interpret the diagnostic model built by Random Forest, the SHapley Additive exPlanations (SHAP) method was employed, and features were ranked according to their SHAP values. Based on these rankings, a diagnostic nomogram was further constructed and the accuracy of the diagnostic model was evaluated using ROC curves. RESULT: After PSM, among the 282 included patients with NAFLD, 141 cases (50%) were complicated with CHD. Multivariate logistic regression analysis revealed that after adjusting for age, sex, hypertension, and smoking history, the NHR index was identified as the most significant risk factor for CHD in NAFLD patients (OR, 1.375; 95% CI, 1.021-1.852; P < 0.001). Additionally, NLR, SII, SIRI and NMR were also identified as risk factors. PNR was a protective factor for CHD events in patients with NAFLD. RCS analysis demonstrated linear relationships between the NHR, NLR, and PNR index with CHD occurrence, whereas the SII index exhibited a non-linear J-shaped relationship with CHD risk (non-linear P = 0.025). Correlation analysis with Gensini score showed that the NHR index had the highest correlation with the severity of CHD (R = 0.256, P < 0.001). ROC curves indicated that the NHR index had good predictive and diagnostic performance (AUC = 0.703,95% CI, 0.652-0.754). Finally, the diagnostic nomogram constructed based on SHAP values demonstrated good accuracy and predictive performance (AUC = 0.834,95% CI, 0.795-0.873; P < 0.001). CONCLUSION: Six immunoinflammatory markers demonstrated significant associations with CHD risk in NAFLD populations, among which the NHR index exhibited particularly promising predictive potential.
21Sarcopenia and sarcopenic obesity.PubMed
Kyung Mook Choi
Korean J Intern Med. 2016 Nov;31(6):1054-1060. doi: 10.3904/kjim.2016.193. Epub 2016 Nov 1.
Sarcopenia is an age-associated loss of muscle mass and decline in muscle strength; it is common in older adults and is associated with significant morbidity and mortality. Despite its prevalence, there is currently no universally adopted definition of sarcopenia. In addition to low muscle mass measurements, recent research has recognized the importance of muscle strength and physical performance. Aging induces changes in body composition, such as an increase in visceral fat and reduced muscle mass. Recently, the new concept of sarcopenic obesity has emerged, reflecting a combination of sarcopenia and obesity. The rapidly increasing prevalence and serious consequences of sarcopenic obesity are recognized as a critical public health risk in the aging society. Sarcopenia and obesity share several pathophysiological mechanisms, and they may potentiate each other. The present paper reviews the definitions and techniques used to measure sarcopenia, as well as the health outcomes of sarcopenic obesity. It also highlights the role of diminished muscle mass and strength in cardiometabolic disease mortality. Additional research may be needed to promote the identification and management of sarcopenia and sarcopenic obesity in the elderly population.
22Ectopic and visceral fat deposition in aging, obesity, and idiopathic pulmonary fibrosis: an interconnected role.PubMed
Xiaoyun Cheng, Shuhan Jiang, Boyu Pan, et al.
Lipids Health Dis. 2023 Nov 24;22(1):201. doi: 10.1186/s12944-023-01964-3.
Idiopathic pulmonary fibrosis (IPF) is considered an age-related disease. Age-related changes, along with other factors such as obesity, hormonal imbalances, and various metabolic disorders, lead to ectopic fat deposition (EFD). This accumulation of fat outside of its normal storage sites is associated with detrimental effects such as lipotoxicity, oxidative stress, inflammation, and insulin resistance. This narrative review provides an overview of the connection between ectopic and visceral fat deposition in aging, obesity, and IPF. It also elucidates the mechanism by which ectopic fat deposition in the airways and lungs, pericardium, skeletal muscles, and pancreas contributes to lung injury and fibrosis in patients with IPF, directly or indirectly. Moreover, the review discusses the impact of EFD on the severity of the disease, quality of life, presence of comorbidities, and overall prognosis in IPF patients. The review provides detailed information on recent research regarding representative lipid-lowering drugs, hypoglycemic drugs, and lipid-targeting drugs in animal experiments and clinical studies. This may offer new therapeutic directions for patients with IPF.
23Energy Metabolism Changes and Dysregulated Lipid Metabolism in Postmenopausal Women.PubMed
Seong-Hee Ko, YunJae Jung
Nutrients. 2021 Dec 20;13(12):4556. doi: 10.3390/nu13124556.
Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make postmenopausal women vulnerable to body composition changes, muscle loss, and abdominal obesity; with a sedentary lifestyle, these changes affect overall energy expenditure and basal metabolic rate. In addition, fat redistribution due to hormonal changes leads to changes in body shape. In particular, increased bone marrow-derived adipocytes due to estrogen loss contribute to increased visceral fat in postmenopausal women. Enhanced visceral fat lipolysis by adipose tissue lipoprotein lipase triggers the production of excessive free fatty acids, causing insulin resistance and metabolic diseases. Because genes involved in β-oxidation are downregulated by estradiol loss, excess free fatty acids produced by lipolysis of visceral fat cannot be used appropriately as an energy source through β-oxidation. Moreover, aged women show increased adipogenesis due to upregulated expression of genes related to fat accumulation. As a result, the catabolism of ATP production associated with β-oxidation decreases, and metabolism associated with lipid synthesis increases. This review describes the changes in energy metabolism and lipid metabolic abnormalities that are the background of weight gain in postmenopausal women.
24Sex hormones, appetite and eating behaviour in women.PubMed
Angelica Lindén Hirschberg
Maturitas. 2012 Mar;71(3):248-56. doi: 10.1016/j.maturitas.2011.12.016. Epub 2012 Jan 26.
Sex hormones play essential roles in the regulation of appetite, eating behaviour and energy metabolism and have been implicated in several major clinical disorders in women. Estrogen inhibits food intake, whereas progesterone and testosterone may stimulate appetite. This review describes recent findings concerning interactions between sex hormones and neuroendocrinological mechanisms in the control of appetite and eating in women. Furthermore, we are gaining insights into the roles played by sex hormones in the development of eating disorders and obesity. For instance, androgens may promote bulimia by stimulating appetite and reducing impulse control, a proposal supported by the observation that antiandrogenic treatment attenuates bulimic behaviour. Androgens are also involved in the pathophysiology of abdominal obesity in women. On the other hand, hormone replacement therapy with estrogen counteracts the weight gain and accumulation of abdominal fat associated with the menopausal transition. In conclusion, sex hormones and/or agents that exhibit similar activities may provide novel strategies for the treatment of eating disorders and android obesity, two of the most serious health problems for women today.
25Adipose Tissue Sex Steroids in Postmenopausal Women With and Without Menopausal Hormone Therapy.PubMed
Natalia Hetemäki, Alexandra Robciuc, Veera Vihma, et al.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):511-522. doi: 10.1210/clinem/dgae458.
CONTEXT: The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized. OBJECTIVE: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n = 50) and without (n = 13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction. RESULTS: HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to nonusers. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to nonusers of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users. CONCLUSION: Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT; these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.
26Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women.PubMed
Natalia Hetemäki, Hanna Savolainen-Peltonen, Matti J Tikkanen, et al.
J Clin Endocrinol Metab. 2017 Dec 1;102(12):4588-4595. doi: 10.1210/jc.2017-01474.
CONTEXT: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. OBJECTIVE: We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. RESULTS: Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). CONCLUSIONS: Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.
27Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation.PubMed
Kaleigh Katzer, Jessica L Hill, Kara B McIver, et al.
Int J Mol Sci. 2021 Oct 29;22(21):11720. doi: 10.3390/ijms222111720.
Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.
28Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1.PubMed
Yifan Lv, Fengliang Wang, Yunlu Sheng, et al.
Exp Gerontol. 2022 Jun 15;163:111796. doi: 10.1016/j.exger.2022.111796. Epub 2022 Apr 2.
Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased pro-inflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22 m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERα in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERα/ERβ ratio in VAT, estrogen supplementation mainly worked through ERβ, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.
29Adipose tissue as a linchpin of organismal ageing.PubMed
Tammy T Nguyen, Silvia Corvera
Nat Metab. 2024 May;6(5):793-807. doi: 10.1038/s42255-024-01046-3. Epub 2024 May 23.
Ageing is a conserved biological process, modulated by intrinsic and extrinsic factors, that leads to changes in life expectancy. In humans, ageing is characterized by greatly increased prevalence of cardiometabolic disease, type 2 diabetes and disorders associated with impaired immune surveillance. Adipose tissue displays species-conserved, temporal changes with ageing, including redistribution from peripheral to central depots, loss of thermogenic capacity and expansion within the bone marrow. Adipose tissue is localized to discrete depots, and also diffusely distributed within multiple organs and tissues in direct proximity to specialized cells. Thus, through their potent endocrine properties, adipocytes are capable of modulating tissue and organ function throughout the body. In addition to adipocytes, multipotent progenitor/stem cells in adipose tissue play a crucial role in maintenance and repair of tissues throughout the lifetime. Adipose tissue may therefore be a central driver for organismal ageing and age-associated diseases. Here we review the features of adipose tissue during ageing, and discuss potential mechanisms by which these changes affect whole-body metabolism, immunity and longevity. We also explore the potential of adipose tissue-targeted therapies to ameliorate age-associated disease burdens.
30Distinct adipose progenitor cells emerging with age drive active adipogenesis.PubMed
Guan Wang, Gaoyan Li, Anying Song, et al.
Science. 2025 Apr 25;388(6745):eadj0430. doi: 10.1126/science.adj0430.
Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was indispensable for CP-A adipogenesis and visceral fat expansion. These findings uncover a fundamental mechanism of age-dependent adipose remodeling, offering critical insights into age-related metabolic diseases.
31Adipose Tissue-Derived Mesenchymal Stem Cells.PubMed
Bruce A Bunnell
Cells. 2021 Dec 6;10(12):3433. doi: 10.3390/cells10123433.
The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage; however, that was shattered with the discovery of adipokines. Scientists interested in regenerative medicine then reported that adipose tissue is rich in adult stromal/stem cells. Following these initial reports, adipose stem cells (ASCs) rapidly garnered interest for use as potential cellular therapies. The primary advantages of ASCs compared to other mesenchymal stem cells (MSCs) include the abundance of the tissue source for isolation, the ease of methodologies for tissue collection and cell isolation, and their therapeutic potential. Studies conducted both in vitro and in vivo have demonstrated that ASCs are multipotent, possessing the ability to differentiate into cells of mesodermal origins, including adipocytes, chondrocytes, osteoblast and others. Moreover, ASCs produce a broad array of cytokines, growth factors, nucleic acids (miRNAs), and other macromolecules into the surrounding milieu by secretion or in the context of microvesicles. The secretome of ASCs has been shown to alter tissue biology, stimulate tissue-resident stem cells, change immune cell activity, and mediate therapeutic outcomes. The quality of ASCs is subject to donor-to-donor variation driven by age, body mass index, disease status and possibly gender and ethnicity. This review discusses adipose stromal/stem cell action mechanisms and their potential utility as cellular therapeutics.
32Adipose-tissue Treg cells restrain differentiation of stromal adipocyte precursors to promote insulin sensitivity and metabolic homeostasis.PubMed
Gang Wang, Andrés R Muñoz-Rojas, Raul German Spallanzani, et al.
Immunity. 2024 Jun 11;57(6):1345-1359.e5. doi: 10.1016/j.immuni.2024.04.002. Epub 2024 Apr 30.
Regulatory T (Treg) cells in epidydimal visceral adipose tissue (eVAT) of lean mice and humans regulate metabolic homeostasis. We found that constitutive or punctual depletion of eVAT-Treg cells reined in the differentiation of stromal adipocyte precursors. Co-culture of these precursors with conditional medium from eVAT-Treg cells limited their differentiation in vitro, suggesting a direct effect. Transcriptional comparison of adipocyte precursors, matured in the presence or absence of the eVAT-Treg-conditioned medium, identified the oncostatin-M (OSM) signaling pathway as a key distinction. Addition of OSM to in vitro cultures blocked the differentiation of adipocyte precursors, while co-addition of anti-OSM antibodies reversed the ability of the eVAT-Treg-conditioned medium to inhibit in vitro adipogenesis. Genetic depletion of OSM (specifically in Treg) cells or of the OSM receptor (specifically on stromal cells) strongly impaired insulin sensitivity and related metabolic indices. Thus, Treg-cell-mediated control of local progenitor cells maintains adipose tissue and metabolic homeostasis, a regulatory axis seemingly conserved in humans.
33Aging-dependent regulatory cells emerge in subcutaneous fat to inhibit adipogenesis.PubMed
Hai P Nguyen, Frances Lin, Danielle Yi, et al.
Dev Cell. 2021 May 17;56(10):1437-1451.e3. doi: 10.1016/j.devcel.2021.03.026. Epub 2021 Apr 19.
Adipose tissue mass and adiposity change throughout the lifespan. During aging, while visceral adipose tissue (VAT) tends to increase, peripheral subcutaneous adipose tissue (SAT) decreases significantly. Unlike VAT, which is linked to metabolic diseases, including type 2 diabetes, SAT has beneficial effects. However, the molecular details behind the aging-associated loss of SAT remain unclear. Here, by comparing scRNA-seq of total stromal vascular cells of SAT from young and aging mice, we identify an aging-dependent regulatory cell (ARC) population that emerges only in SAT of aged mice and humans. ARCs express adipose progenitor markers but lack adipogenic capacity; they secrete high levels of pro-inflammatory chemokines, including Ccl6, to inhibit proliferation and differentiation of neighboring adipose precursors. We also found Pu.1 to be a driving factor for ARC development. We identify an ARC population and its capacity to inhibit differentiation of neighboring adipose precursors, correlating with aging-associated loss of SAT.
34Short-term Dietary Interventions for the Management of Nonalcoholic Fatty Liver.PubMed
Caroline S Stokes, Frank Lammert, Marcin Krawczyk
Curr Med Chem. 2019;26(19):3483-3496. doi: 10.2174/0929867324666170508144409.
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects millions of individuals on a global scale and currently no gold standard treatment exists. The risk of developing NAFLD is considerably higher with increasing body mass index. Consequently, weight loss should be recommended to all overweight patients with fatty liver. However, lifestyle interventions, irrespective of weight status, may also influence the condition. The aim herein is to present examples of short-term interventions which assess direct effects of dietary-related components on hepatic steatosis. METHODS: This review includes studies with short-term dietary-related interventions of up to 16 weeks that evaluate their efficacy in reducing intrahepatic lipid contents (hepatic steatosis). This review primarily focuses on the three main macronutrients: dietary carbohydrates, fats and proteins. RESULTS: High saturated fat intake and high consumption of carbohydrates, particularly from simple sugars such as fructose are reported as risk factors for hepatic steatosis. Overall, shortterm hypocaloric diets have shown beneficial effects in reducing intrahepatic lipid contents. Macronutrient manipulations such as carbohydrate restriction as well as the consumption of unsaturated fatty acids are also reported to have efficacious effects. CONCLUSION: This review highlights the different dietary interventions that can influence hepatic steatosis in the short term, illustrating both pro and anti-steatotic effects.
35Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance.PubMed
Hannele Yki-Järvinen
Nutrients. 2015 Nov 5;7(11):9127-38. doi: 10.3390/nu7115454.
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%-23% fat and 57%-65% carbohydrate lower liver fat compared to diets with 43%-55% fat and 27%-38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.
36Is non-alcoholic fatty liver disease a reflection of what we eat or simply how much we eat?PubMed
Kiri P H Sharp, Michael Schultz, Kirsten J Coppell
JGH Open. 2018 Mar 2;2(2):59-74. doi: 10.1002/jgh3.12040. eCollection 2018 Apr.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common and potentially serious condition, which has emerged with the obesity epidemic. This disease can progress to cirrhosis and hepatocellular cancer. Associated comorbidities, such as cardiovascular disease and type 2 diabetes, are common. Obesity is the key risk factor and diet appears to be a critical factor in the pathogenesis of NAFLD. We reviewed studies undertaken on human subjects investigating which dietary components initiate excess hepatic triglyceride deposition. Most experimental diets used high-calorie excesses, or extreme proportions of fat or carbohydrate, not typical of current dietary patterns. Hypercaloric diets, where the additional calories were predominantly either fat or carbohydrates, increased intrahepatocellular lipids. The type of fat appeared important, with diets high in saturated fatty acids favoring hepatic fat accumulation which was substantially lower with polyunsaturated fatty acids. The effect of dietary fructose on markers of NAFLD did not appear to be worse than that of glucose. The initiation of excess hepatic triglycerides is likely to be a complex interaction of energy and nutrients with more than one dietary factor involved. It was not possible to disentangle the hepatic effects of excess energy from that of different macronutrient distributions in current literature. Further investigation is needed to determine the type of diet that is likely to lead to the development of NAFLD. A better understanding of the contribution of diet to pathogenesis of NAFLD would better inform prevention strategies.
37GPAM upregulation enhances hepatic fat deposition and reduces visceral adipose tissue in response to trans-fatty acids.PubMed
Teruki Miyake, Osamu Yoshida, Shinya Furukawa, et al.
J Gastroenterol. 2025 Dec;60(12):1554-1571. doi: 10.1007/s00535-025-02297-x. Epub 2025 Oct 4.
BACKGROUND: Dietary fatty acids are involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). We examined the mechanism by which dietary fatty acid composition affects MASLD pathogenesis. METHODS: The MASLD mouse model was developed by feeding a high-fat diet (HFD) rich in palmitic acid (PA), trans-fatty acids (TFAs), or oleic acid (OA). For in vitro experiments, Hepa 1-6 cells were exposed to PA, elaidic acid (a representative TFA), and OA. Glycerol-3-phosphate acyltransferase 1 (GPAM) expression in Hepa 1-6 cells was manipulated using a plasmid encoding GPAM and GPAM-specific siRNAs. In addition, GPAM depletion in the liver of HFD-fed mice was achieved using a pH-sensitive multifunctional envelope-type nanodevice as a siRNA carrier. Liver specimens from patients with MASLD were also analyzed. RESULTS: The TFA group displayed higher serum alanine-aminotransferase and hepatic triglyceride content but lower serum fasting triglyceride and visceral adipose tissue (VAT) compared with that in the PA and OA groups. Hepatic GPAM expression in the TFA group was higher than in the PA group. Consistently, TFA-treated Hepa 1-6 cells showed a greater GPAM increase than that with OA and PA. GPAM-overexpressing Hepa 1-6 cells showed increased triglyceride accumulation, whereas GPAM-deficient cells failed to accumulate triglyceride. Hepatic GPAM knockdown in HFD-fed mice suppressed steatosis and increased VAT. Notably, hepatic GPAM gene expression was higher in patients with severe steatosis than in those with non-severe steatosis. CONCLUSIONS: A TFA-rich HFD increased hepatic GPAM expression, exacerbated steatosis, and decreased VAT. Therefore, GPAM may regulate systemic fat accumulation in the body.
38The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.PubMed
Seema Sharma, Nishant Tiwari, Sampat Singh Tanwar
Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep;398(9):11541-11579. doi: 10.1007/s00210-025-04069-z. Epub 2025 Apr 9.
Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.
39Association of the COVID-19 pandemic with changes in objectively measured sedentary behaviour and adiposity.PubMed
Keita Kinoshita, Naoki Ozato, Tohru Yamaguchi, et al.
Int J Obes (Lond). 2023 May;47(5):375-381. doi: 10.1038/s41366-023-01274-9. Epub 2023 Feb 16.
BACKGROUND: Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors. METHODS: Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes. RESULTS: Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (β = 3.85, 95% CI 1.22-6.49, P = 0.004) and a decrease in adiponectin level (β = -0.04, 95% CI -0.06 to -0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA. CONCLUSIONS: The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic.
40Association between Objectively Measured Sedentary Behaviour and Sleep Quality in Japanese Adults: A Population-Based Cross-Sectional Study.PubMed
Keita Kinoshita, Naoki Ozato, Tohru Yamaguchi, et al.
Int J Environ Res Public Health. 2022 Mar 7;19(5):3145. doi: 10.3390/ijerph19053145.
The association between sedentary behaviour and sleep quality (SQ) remains unclear, partly due to the limited methodology for assessing sedentary time and the influence of obesity. This study aimed to examine the association between objectively measured sedentary time and poor SQ, as well as the association of visceral fat accumulation. This cross-sectional study used health check-up data obtained from 721 Japanese adults. Sedentary time and physical activity were measured using an accelerometer for ≥7 days, with ≥10 measurement hours per day. Poor SQ was determined by a Pittsburgh Sleep Quality Index score of ≥ 6. Visceral fat was measured using the abdominal bioimpedance method. A logistic regression model was used to analyse the association between sedentary time and SQ. We found that higher sedentary time was associated with poorer SQ. This association remained significant after adjustment for several covariates, including visceral fat. Compared with the lowest tertile of sedentary time, the second and highest tertile had a significantly higher OR of poor SQ (Tertile 2: OR = 2.06 [95% CI 1.14,3,73]; Tertile 3: OR = 2.76 [95% CI 1.49, 5.11]). These results suggest that managing sedentary time itself might contribute to improving SQ.
41Incidental physical activity and sedentary behavior are not associated with abdominal adipose tissue in inactive adults.PubMed
K Ashlee McGuire, Robert Ross
Obesity (Silver Spring). 2012 Mar;20(3):576-82. doi: 10.1038/oby.2011.278. Epub 2011 Sep 29.
The aim was to determine the association between objectively measured incidental physical activity (IPA) (i.e.,nonpurposeful activity accrued through activities of daily living) and sedentary behavior (SED) with abdominal obesity in a sample of inactive men and women. Participants were inactive, abdominally obese men (n = 42; waist circumference (WC) ≥102 cm) and women (n = 84; WC ≥88 cm) recruited from Kingston, Canada. Physical activity and SED were determined by accelerometry over 7 days and summarized as IPA (accelerometer counts per min (cpm) >100), light physical activity (LPA; cpm 100-1951), sporadic moderate-to-vigorous physical activity (MVPA; cpm ≥1,952, accumulated in bouts <10 consecutive minutes) and SED (cpm <100). Magnetic resonance imaging was used to acquire measures of abdominal obesity, visceral adipose tissue (VAT), and subcutaneous adipose tissue (ASAT). Participants spent on average 310.2 ± 102.6 min/d in IPA and 627.8 ± 86.9 min/d in SED. Neither IPA nor SED was associated with any measure of abdominal obesity (P > 0.1). Similarly, LPA was not a significant predictor of abdominal obesity whereas sporadic MVPA was negatively associated with VAT (P < 0.05) after control for age and sex. In this study, neither IPA nor SED was associated with abdominal obesity among inactive men and women.
42A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice.PubMed
Huijing Liang, Fengling Jiang, Ruyue Cheng, et al.
Exp Anim. 2021 Feb 6;70(1):73-83. doi: 10.1538/expanim.20-0094. Epub 2020 Oct 1.
This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.
43Gut Microbiota-Butyrate-PPARγ Axis Modulates Adipose Regulatory T Cell Population.PubMed
Banru Chen, Lizhi Guan, Chao Wu, et al.
Adv Sci (Weinh). 2025 May;12(20):e2411086. doi: 10.1002/advs.202411086. Epub 2025 Feb 25.
Gut microbiota is essential for the function of peripherally-induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat-resident Treg cells that harbor a unique expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2 Treg), which are largely restored after gut microbiome reconstruction. Mechanistically, gut microbiota-derived butyrate increases VAT ST2 Treg cells through binding PPARγ. Butyrate supplementation and high fiber diet increase VAT ST2 Treg population in obese mice, and ameliorated glucose tolerance and visceral inflammation. Furthermore, human omental adipose Treg cells show positive correlation with fecal butyrate and certain butyrate-producing microbes. This study identifies the critical role of gut microbiota-butyrate-PPARγ axis in maintaining VAT Treg population, pinpointing a potential approach to augment VAT Treg population and ameliorate inflammation.
44Butyrate and tributyrin reduce LPS-induced inflammatory cytokine production from human visceral fat.PubMed
Hossein Rafiei, Michelle Yeung, Sara Kowalski, et al.
Int J Obes (Lond). 2024 Nov;48(11):1559-1567. doi: 10.1038/s41366-024-01581-9. Epub 2024 Jul 10.
INTRODUCTION: The current obesity crisis has resulted in many people with excess adipose tissue suffering from chronic inflammation. This inflammation is largely due to the release of cytokines and chemokines from visceral fat. The aim of this study was to identify potential anti-inflammatory agents that might alleviate obesity-induced chronic inflammation. METHODS: To identify agents that might alleviate this obesity-induced chronic inflammation we have developed a simple protocol for incubating intact pieces of human visceral adipose tissue in 35 mm tissue culture plates, in the presence of low-dose lipopolysaccharide (LPS) and co-incubating these samples with potential anti-inflammatory agents. RNA-Seq analysis was performed to identify enriched gene expression signatures among the most significantly differentially expressed genes. RESULTS: From this screen, we have identified the short-chain fatty acid (SCFA) sodium butyrate and its triacylglyceride form, tributyrin, as effective agents, significantly reducing the production of LPS-induced inflammatory cytokines and chemokines from all adipose tissue samples tested. As well, these agents appear to be non-toxic at the concentrations tested. RNA-Seq analysis has revealed that IL36γ is one of the most upregulated genes in response to LPS and one of the most downregulated when sodium butyrate is added to human fat samples stimulated with LPS. IL-36γ ELISAs confirmed this holds true at the protein level as well. CONCLUSIONS: These studies suggest that the short-chain fatty acid, sodium butyrate, and its triacylglyceride form, tributyrin, might alleviate the chronic inflammation that is associated with many individuals with obesity.
45Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects.PubMed
Shaun Eslick, Evan J Williams, Bronwyn S Berthon, et al.
Nutrients. 2022 Feb 11;14(4):765. doi: 10.3390/nu14040765.
BACKGROUND: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. METHODS: Blood samples were collected from 43 obese subjects (BMI ≥ 30 kg/m) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12-18 months post-surgery and 8 healthy weight subjects (BMI 18.5-24.9 kg/m). Monocytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were harvested after 15 h incubation. TNF-α and IL-6 cytokines were measured via ELISA and mRNA gene expression of and , , and , and and via RT-qPCR. RESULTS: TNF-α and IL-6 production and and mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α and IL-6 and altered and mRNA expression in monocytes and macrophages from obese subjects. CONCLUSION: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.
46Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils.PubMed
Dharti Shantaram, Rebecca Hoyd, Alecia M Blaszczak, et al.
Nat Commun. 2024 Jun 27;15(1):5434. doi: 10.1038/s41467-024-48935-5.
Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.
47Effects of a Low-Fat Vegan Diet on Gut Microbiota in Overweight Individuals and Relationships with Body Weight, Body Composition, and Insulin Sensitivity. A Randomized Clinical Trial.PubMed
Hana Kahleova, Emilie Rembert, Jihad Alwarith, et al.
Nutrients. 2020 Sep 24;12(10):2917. doi: 10.3390/nu12102917.
Diet modulates gut microbiota and plays an important role in human health. The aim of this study was to test the effect of a low-fat vegan diet on gut microbiota and its association with weight, body composition, and insulin resistance in overweight men and women. We enrolled 168 participants and randomly assigned them to a vegan ( = 84) or a control group ( = 84) for 16 weeks. Of these, 115 returned all gut microbiome samples. Gut microbiota composition was assessed using uBiome Explorer™ kits. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was quantified with the predicted clamp-derived insulin sensitivity index from a standard meal test. Repeated measure ANOVA was used for statistical analysis. Body weight decreased in the vegan group (treatment effect -5.9 kg [95% CI, -7.0 to -4.9 kg]; < 0.001), mainly due to a reduction in fat mass (-3.9 kg [95% CI, -4.6 to -3.1 kg]; < 0.001) and in visceral fat (-240 cm [95% CI, -345 to -135 kg]; < 0.001). PREDIcted M, insulin sensitivity index (PREDIM) increased in the vegan group (treatment effect +0.83 [95% CI, +0.48 to +1.2]; < 0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (+5.1% [95% CI, +2.4 to +7.9%]; < 0.001) and correlated negatively with changes in weight (r = -0.24; = 0.01), fat mass (r = -0.22; = 0.02), and visceral fat (r = -0.20; = 0.03). The relative abundance of Bacteroides fragilis decreased in both groups, but less in the vegan group, making the treatment effect positive (+18.9% [95% CI, +14.2 to +23.7%]; < 0.001), which correlated negatively with changes in weight (r = -0.44; < 0.001), fat mass (r = -0.43; < 0.001), and visceral fat (r = -0.28; = 0.003) and positively with PREDIM (r = 0.36; < 0.001), so a smaller reduction in Bacteroides fragilis was associated with a greater loss of body weight, fat mass, visceral fat, and a greater increase in insulin sensitivity. A low-fat vegan diet induced significant changes in gut microbiota, which were related to changes in weight, body composition, and insulin sensitivity in overweight adults, suggesting a potential use in clinical practice.
48Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia.PubMed
Xiaolin Ye, Yang Liu, Jiajin Hu, et al.
Front Endocrinol (Lausanne). 2021 Dec 16;12:762691. doi: 10.3389/fendo.2021.762691. eCollection 2021.
BACKGROUND: Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia. METHOD: Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation. RESULTS: CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., , , , and ) and , which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia. CONCLUSION: CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.
49Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: a classical twin study.PubMed
A L Jermendy, M Kolossvary, Z D Drobni, et al.
Int J Obes (Lond). 2018 Feb;42(2):163-168. doi: 10.1038/ijo.2017.212. Epub 2017 Aug 30.
BACKGROUND/OBJECTIVES: Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs. SUBJECTS/METHODS: In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models. RESULTS: In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (r=0.81, r=0.32), similar to SAT and VAT quantities (r=0.80, r=0.68 and r=0.79, r=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two. CONCLUSIONS: Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.
50Genetic variants influencing obesity-related traits in Japanese population.PubMed
Kazuhiro Nakayama, Yuta Inaba
Ann Hum Biol. 2019 Jun;46(4):298-304. doi: 10.1080/03014460.2019.1644373. Epub 2019 Aug 9.
Adipose tissue is the main organ that stores energy and participates in adaptive thermogenesis of the human body. The adipose tissue content in an individual is determined by a combination of genetic factors and lifestyle related factors. While Japanese people, along with the closely related East Asians, are generally thinner than individuals of European ancestry, they are prone to accumulating visceral adipose tissues. Genome-wide discovery of loci influencing obesity-related traits, and application of the genome sequence data to assess natural selection, provides evidence that the obesity-related traits in East Asians might be shaped by natural selection. This review aims to summarise health and evolutionary implications of genetic variants influencing obesity-related traits in Japanese. This study gathered recently published papers of medical, genetic and evolutionary studies regarding obesity-related traits in the Japanese and closely related East Asians. A high susceptibility to central obesity of Japanese and closely related East Asians might have been shaped by natural selection favouring thrifty genotypes. Moreover, natural selection favouring higher thermogenic activity of brown adipose tissues would contribute to increased non-thrifty alleles in ancestors of East Asians.
51Single nucleus RNA-sequencing integrated into risk variant colocalization discovers 17 cell-type-specific abdominal obesity genes for metabolic dysfunction-associated steatotic liver disease.PubMed
Seung Hyuk T Lee, Kristina M Garske, Uma Thanigai Arasu, et al.
EBioMedicine. 2024 Aug;106:105232. doi: 10.1016/j.ebiom.2024.105232. Epub 2024 Jul 10.
BACKGROUND: Abdominal obesity increases the risk for non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: To elucidate the directional cell-type level biological mechanisms underlying the association between abdominal obesity and MASLD, we integrated adipose and liver single nucleus RNA-sequencing and bulk cis-expression quantitative trait locus (eQTL) data with the UK Biobank genome-wide association study (GWAS) data using colocalization. Then we used colocalized cis-eQTL variants as instrumental variables in Mendelian randomization (MR) analyses, followed by functional validation experiments on the target genes of the cis-eQTL variants. FINDINGS: We identified 17 colocalized abdominal obesity GWAS variants, regulating 17 adipose cell-type marker genes. Incorporating these 17 variants into MR discovers a putative tissue-of-origin, cell-type-aware causal effect of abdominal obesity on MASLD consistently with multiple MR methods without significant evidence for pleiotropy or heterogeneity. Single cell data confirm the adipocyte-enriched mean expression of the 17 genes. Our cellular experiments across human adipogenesis identify risk variant -specific epigenetic and transcriptional mechanisms. Knocking down two of the 17 genes, PPP2R5A and SH3PXD2B, shows a marked decrease in adipocyte lipidation and significantly alters adipocyte function and adipogenesis regulator genes, including DGAT2, LPL, ADIPOQ, PPARG, and SREBF1. Furthermore, the 17 genes capture a characteristic MASLD expression signature in subcutaneous adipose tissue. INTERPRETATION: Overall, we discover a significant cell-type level effect of abdominal obesity on MASLD and trace its biological effect to adipogenesis. FUNDING: NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foundation for Cardiovascular Research the Sigrid Jusélius Foundation and the Jane and Aatos Erkko Foundation; American Association for the Study of Liver Diseases (AASLD) Advanced Transplant Hepatology award and NIH/NIDDK (P30DK41301) Pilot and Feasibility award; NIH/NIEHS F32 award (F32ES034668); Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2021), the Academy of Finland grant (Contract no. 138006); Academy of Finland (Grant Nos 335443, 314383, 272376 and 266286), Sigrid Jusélius Foundation, Finnish Medical Foundation, Finnish Diabetes Research Foundation, Novo Nordisk Foundation (#NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) and Government Research Funds to Helsinki University Hospital; Orion Research Foundation, Maud Kuistila Foundation, Finish Medical Foundation, and University of Helsinki.
52Mechanisms and risk factors of metabolic syndrome in children and adolescents.PubMed
Valentina Codazzi, Giulio Frontino, Luca Galimberti, et al.
Endocrine. 2024 Apr;84(1):16-28. doi: 10.1007/s12020-023-03642-x. Epub 2023 Dec 22.
Metabolic syndrome (MetS) is a complex disorder characterized by abdominal obesity, elevated blood pressure, hyperlipidemia, and elevated fasting blood glucose levels. The diagnostic criteria for MetS in adults are well-established, but there is currently no consensus on the definition in children and adolescents. The etiology of MetS is believed to involve a complex interplay between genetic predisposition and environmental factors. While genetic predisposition explains only a small part of MetS pathogenesis, modifiable environmental risk factors play a significant role. Factors such as maternal weight during pregnancy, children's lifestyle, sedentariness, high-fat diet, fructose and branched-chain amino acid consumption, vitamin D deficiency, and sleep disturbances contribute to the development of MetS. Early identification and treatment of MetS in children and adolescents is crucial to prevent the development of chronic diseases later in life. In this review we discuss the latest research on factors contributing to the pathogenesis of MetS in children, focusing on non-modifiable and modifiable risk factors, including genetics, dysbiosis and chronic low-grade inflammation.
53Insufficient sleep undermines dietary efforts to reduce adiposity.PubMed
Arlet V Nedeltcheva, Jennifer M Kilkus, Jacqueline Imperial, et al.
Ann Intern Med. 2010 Oct 5;153(7):435-41. doi: 10.7326/0003-4819-153-7-201010050-00006.
BACKGROUND: Sleep loss can modify energy intake and expenditure. OBJECTIVE: To determine whether sleep restriction attenuates the effect of a reduced-calorie diet on excess adiposity. DESIGN: Randomized, 2-period, 2-condition crossover study. SETTING: University clinical research center and sleep laboratory. PATIENTS: 10 overweight nonsmoking adults (3 women and 7 men) with a mean age of 41 years (SD, 5) and a mean body mass index of 27.4 kg/m² (SD, 2.0). INTERVENTION: 14 days of moderate caloric restriction with 8.5 or 5.5 hours of nighttime sleep opportunity. MEASUREMENTS: The primary measure was loss of fat and fat-free body mass. Secondary measures were changes in substrate utilization, energy expenditure, hunger, and 24-hour metabolic hormone concentrations. RESULTS: Sleep curtailment decreased the proportion of weight lost as fat by 55% (1.4 vs. 0.6 kg with 8.5 vs. 5.5 hours of sleep opportunity, respectively; P = 0.043) and increased the loss of fat-free body mass by 60% (1.5 vs. 2.4 kg; P = 0.002). This was accompanied by markers of enhanced neuroendocrine adaptation to caloric restriction, increased hunger, and a shift in relative substrate utilization toward oxidation of less fat. LIMITATION: The nature of the study limited its duration and sample size. CONCLUSION: The amount of human sleep contributes to the maintenance of fat-free body mass at times of decreased energy intake. Lack of sufficient sleep may compromise the efficacy of typical dietary interventions for weight loss and related metabolic risk reduction. PRIMARY FUNDING SOURCE: National Institutes of Health.
54Association between obstructive sleep apnea and visceral adiposity index and lipid accumulation product: NHANES 2015-2018.PubMed
Tingfeng Zhou, Shihao Chen, Jiesheng Mao, et al.
Lipids Health Dis. 2024 Apr 10;23(1):100. doi: 10.1186/s12944-024-02081-5.
BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.
55Neuropeptide Y gene-by-psychosocial stress interaction effect is associated with obesity in a Korean population.PubMed
Hyun-Jin Kim, Kyoung-Bok Min, Jin-Young Min
Psychoneuroendocrinology. 2016 Jul;69:10-5. doi: 10.1016/j.psyneuen.2016.03.003. Epub 2016 Mar 7.
BACKGROUND: Chronic psychosocial stress is a crucial risk factor in the development of many diseases including obesity. Neuropeptide Y (NPY), distributed throughout the peripheral and central nervous system, is believed to pay a role in the pathophysiologic relationship between stress and obesity. Although several animal studies have investigated the impact on obesity of interactions between NPY single nucleotide polymorphisms (SNPs) and stress, the same remains to be analyzed in humans. METHODS: To identify NPY gene-by-stress interaction effects on human obesity, we analyzed the interaction between four NPY SNPs and stress with obesity-related traits, including visceral adipose tissue (VAT). A total of 1468 adult subjects were included for this analysis. RESULTS: In a SNP-only model without interaction with stress, no significant SNPs were found (pSNP>0.05). However, NPY SNPs-by-stress interaction effects were significantly linked to body mass index (BMI), waist circumference, and VAT (pint<0.05), even though a significant interaction effect for rs16135 on BMI was not identified. These significant interaction effects were also detected in interaction results for the binary traits of obesity. Among the obesity traits, mean changes of VAT by increased stress levels in homozygous risk allele carriers were the greatest (range of mean increases for four SNPs (min-max)=12.57cm(2)-29.86cm(2)). CONCLUSIONS: This study suggests that common polymorphisms for NPY were associated with human obesity by interacting with psychosocial stress, emphasizing the need for stress management in obesity prevention.
56Increased Diet Quality is Associated with Long-Term Reduction of Abdominal and Pericardial Fat.PubMed
Rachel Hennein, Chunyu Liu, Nicola M McKeown, et al.
Obesity (Silver Spring). 2019 Apr;27(4):670-677. doi: 10.1002/oby.22427. Epub 2019 Mar 1.
OBJECTIVE: This study examined the longitudinal associations between genetic risk, change in diet quality, and change in visceral adipose tissue (ΔVAT), abdominal subcutaneous adipose tissue (ΔSAT), and pericardial adipose tissue (ΔPAT). METHODS: A total of 1,677 Framingham Heart Study participants who had ectopic fat depots measured using computed tomography were analyzed. Diet quality was quantified using a Mediterranean-style diet score (MDS) and genetic risk by depot-specific genetic risk scores (GRSs). RESULTS: Per SD improvement in MDS, there was 50 cm (95% CI: 14-86; P = 0.007) less fat accumulation in VAT, 52 cm (95% CI: 12-92; P = 0.01) less fat accumulation in SAT, and 1.3 cm (95% CI: 0.1-2.4; P = 0.04) less fat accumulation in PAT. No association was observed between GRSs and ΔVAT or ΔSAT. Each 1-SD increase in the PAT GRS was associated with a 1.2-cm (95% CI: 0.1-2.3; P = 0.03) increase in ΔPAT. In participants with higher PAT GRS, those with ΔMDS ≥ 0 had a favorable change in PAT compared with the counterparts with ΔMDS < 0 (P = 0.008). CONCLUSIONS: Longitudinal improvements in diet quality are associated with less ectopic fat accumulation. This study suggests that diet quality may play a critical role in improving ectopic adiposity profiles.
57Comparison of the effects of six-week time-restricted eating on weight loss, body composition, and visceral fat in overweight older men and women.PubMed
Przemysław Domaszewski, Mariusz Konieczny, Tomasz Dybek, et al.
Exp Gerontol. 2023 Apr;174:112116. doi: 10.1016/j.exger.2023.112116. Epub 2023 Feb 3.
The aim of this study was to determine the effectiveness of a six-week time-restricted eating (TRE) intervention in reducing body weight, fat loss, and visceral fat in overweight, older adult men and women (age range = 65-74 years). Another objective was to determine the feasibility of widespread use of TRE in older women and men. The study randomly assigned 116 healthy, non-smoking participants to one of two conditions: TRE or educational control participants. Participants in the TRE group were instructed to not consume calorie containing beverages or food for 16 h per day, from 8:00 pm to 12:00 pm. Participants in the control group were instructed to follow a meal plan based on their previous habits. The changes in body weight and body composition were determined using a SECA mBCA 515 analyzer. The six-week TRE intervention resulted in a significant decrease in body weight in both men and women (-1.8 kg and-1.3 kg, respectively; p = 0.03). In men, a significant decrease in visceral fat mass (-0.54 l; p ≤ 0.001) and waist circumference (-2.9 cm; p ≤ 0.015) was observed. No significant changes in either visceral fat or waist circumference were observed in women. Additionally, no change in skeletal muscle mass was observed in either the control or TRE group. More than 99 % of female and 98 % of male participants were able to adhere to the prescribed time-restricted eating (16/8) plan, suggesting that this dietary approach could have beneficial effects on the body composition of overweight older men and may also reduce body weight in overweight, older women.
58High-Protein Time-Restricted Eating Alongside Resistance Training Reduces Adipose Tissue While Preserving Fat-Free Mass in Women With Overweight: A Randomized Controlled Trial.PubMed
Fatemeh Bagherpour, Hamid Arazi, Hamid Rajabi, et al.
Int J Sport Nutr Exerc Metab. 2025 Aug 11;35(6):493-509. doi: 10.1123/ijsnem.2025-0010. Print 2025 Nov 1.
BACKGROUND: Time-restricted eating (TRE), a subtype of intermittent fasting, has gained significant popularity in recent years. This dietary approach, when combined with resistance training (RT), has demonstrated potential benefits for body composition and physiological parameters. OBJECTIVE: This study aimed to investigate the effects of TRE and high-protein consumption on visceral adipose tissue (VAT), subcutaneous adipose tissue, leptin, and ghrelin levels in young women with overweight engaged in RT. METHODS: Thirty-two women with overweight (body mass index 25-30 kg/m2), aged 18-30 years, were randomly assigned to four groups: TRE with high protein (THP), TRE with regular protein, high protein only (HP), and regular protein only. All participants underwent RT and adhered to a 25% calorie-restricted diet. The high-protein groups received 1.6 g·kg-1·day-1 of protein. Body composition, blood biomarkers, and muscle functions were assessed. RESULTS: Significant reductions in VAT (p < .001) and subcutaneous adipose tissue (p < .001) were observed across all groups, with the THP group exhibiting the greatest decrease in VAT (Δ = -146.98 ± 12.66, d = -1.867). Leptin levels also showed a significant decrease in all groups (p < .001). However, significant differences in leptin reduction were detected only between THP versus regular protein only (p = .045) and TRE with regular protein versus regular protein only (p = .034) groups. Plasma ghrelin levels remained unchanged across all groups. Notably, the high-protein groups (THP and high protein only) demonstrated a significant increase in fat-free mass (Δ THP = 1.06 ± 1.75, Δ HP = 2.37 ± 0.64). CONCLUSION: An 8-week program combining TRE, high-protein intake, and RT effectively reduced VAT, subcutaneous adipose tissue, and leptin levels while preserving muscle mass in women with overweight. This intervention did not significantly alter plasma ghrelin levels.
59Alternate Day Fasting Combined with a Low Carbohydrate Diet: Effect on Sleep Quality, Duration, Insomnia Severity and Risk of Obstructive Sleep Apnea in Adults with Obesity.PubMed
Faiza Kalam, Kelsey Gabel, Sofia Cienfuegos, et al.
Nutrients. 2021 Jan 13;13(1):211. doi: 10.3390/nu13010211.
: Alternate day fasting combined with a low carbohydrate diet (ADF-LC) is an effective weight loss regimen. Whether the weight loss induced by ADF-LC can improve sleep, remains unknown. Objective: This study examined the effect an ADF-LC diet on sleep quality, duration, insomnia severity and the risk of obstructive sleep apnea. : Adults with obesity ( = 31) participated in ADF (600 kcal "fast day"; ad libitum intake "feast day") with a low-carbohydrate diet (30% carbohydrates, 35% protein, and 35% fat). The 6-month trial consisted of a 3-month weight loss period followed by a 3-month weight maintenance period. : Reductions in body weight (-5 ± 1 kg, < 0.001) and fat mass (-4 ± 1 kg, < 0.01) were noted during the weight loss period, and these reductions were sustained during the weight maintenance period. Lean mass and visceral fat remained unchanged. The Pittsburgh Sleep Quality Index (PSQI) score indicated poor sleep quality at baseline (6.4 ± 0.7) with no change by month 3 or 6, versus baseline. ISI score indicated subthreshold insomnia at baseline (8.5 ± 1.0), with no change by month 3 or 6, versus baseline. The percent of subjects with high risk of obstructive sleep apnea at baseline was 45%, with no change by month 3 or 6. Wake time, bedtime, and sleep duration remained unchanged. : The ADF-LC diet does not impact sleep quality, duration, insomnia severity or the risk of obstructive sleep apnea in adults with obesity.
60Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.PubMed
Manuel Dote-Montero, Elisa Merchan-Ramirez, Maddi Oses, et al.
Nutr Metab Cardiovasc Dis. 2024 Jan;34(1):177-187. doi: 10.1016/j.numecd.2023.09.014. Epub 2023 Sep 21.
BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.
61Dietary Strategies for Metabolic Syndrome: A Comprehensive Review.PubMed
Sara Castro-Barquero, Ana María Ruiz-León, Maria Sierra-Pérez, et al.
Nutrients. 2020 Sep 29;12(10):2983. doi: 10.3390/nu12102983.
Metabolic syndrome is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, low levels of high-density lipoprotein cholesterol (HDL-c), hypertension, and insulin resistance. Lifestyle modifications, especially dietary habits, are the main therapeutic strategy for the treatment and management of metabolic syndrome, but the most effective dietary pattern for its management has not been established. Specific dietary modifications, such as improving the quality of the foods or changing macronutrient distribution, showed beneficial effects on metabolic syndrome conditions and individual parameters. On comparing low-fat and restricted diets, the scientific evidence supports the use of the Mediterranean Dietary Approaches to Stop Hypertension (DASH) diet intervention as the new paradigm for metabolic syndrome prevention and treatment. The nutritional distribution and quality of these healthy diets allows health professionals to provide easy-to-follow dietary advice without the need for restricted diets. Nonetheless, energy-restricted dietary patterns and improvements in physical activity are crucial to improve the metabolic disturbances observed in metabolic syndrome patients.
62Effects of the Mediterranean Diet on the Components of Metabolic Syndrome Concerning the Cardiometabolic Risk.PubMed
Stefania Scaglione, Tiziana Di Chiara, Mario Daidone, et al.
Nutrients. 2025 Jan 20;17(2):358. doi: 10.3390/nu17020358.
Metabolic syndrome is a cluster of risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia (intended as an increase in triglyceride levels and a reduction in HDL cholesterol levels), and elevated fasting glucose, that increase the risk of cardiovascular disease and type 2 diabetes. With the rising prevalence of metabolic syndrome, effective dietary interventions are essential in reducing these health risks. The Mediterranean diet, rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil and moderate in fish and poultry, has shown promise in addressing metabolic syndrome and its associated components. This diet's anti-inflammatory and antioxidant properties, primarily due to its unsaturated fats, polyphenols, and fiber, have improved blood pressure, lipid levels, and insulin sensitivity. Adherence to the Mediterranean diet has been linked to reductions in central obesity and insulin resistance, both key elements in managing metabolic syndrome. Regarding lipid management, the Mediterranean diet lowers triglyceride levels and low-density lipoprotein (LDL) cholesterol while raising high-density lipoprotein (HDL) cholesterol, enhancing lipid profiles. It also helps regulate blood glucose levels, reducing the likelihood of developing type 2 diabetes. Additionally, the diet promotes weight loss and improves body composition, particularly by decreasing visceral fat, a primary driver of metabolic syndrome according to IDF classification. The Mediterranean diet offers a holistic approach to managing metabolic syndrome and reducing the risk of related chronic diseases. Its positive impact on metabolic health, combined with lifestyle changes like increased physical activity, provides a sustainable method for addressing the global burden of this syndrome. This review aimed to summarize the positive effects of the Mediterranean diet on the component of the metabolic syndrome with subsequent positive effects on cardiometabolic risk profile.
63An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.PubMed
Jadwiga Konieczna, Miguel Ruiz-Canela, Aina M Galmes-Panades, et al.
JAMA Netw Open. 2023 Oct 2;6(10):e2337994. doi: 10.1001/jamanetworkopen.2023.37994.
IMPORTANCE: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN89898870.
64Multidimensional Impact of Mediterranean Diet on IBD Patients.PubMed
Fabio Chicco, Salvatore Magrì, Arianna Cingolani, et al.
Inflamm Bowel Dis. 2021 Jan 1;27(1):1-9. doi: 10.1093/ibd/izaa097.
BACKGROUND & AIMS: Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. METHODS: Patients with IBD, both Crohn's disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. RESULTS: One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC -0.42, P = 0.002; CD -0.48, P = 0.032) and waist circumference (UC -1.25 cm, P = 0.037; CD -1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. CONCLUSIONS: A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers.
65Impact of a Mediterranean-Inspired Diet on Cardiovascular Disease Risk Factors: A Randomized Clinical Trial.PubMed
Ana Rita Barbosa, Sandra Pais, Ana Marreiros, et al.
Nutrients. 2024 Jul 26;16(15):2443. doi: 10.3390/nu16152443.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. This study focused on evaluating the impact of a Mediterranean-type diet combined with physical exercise on CVD risk factors of high-risk individuals. A randomized clinical trial (RCT) recruited individuals (≥50 years old) with no history of acute myocardial infarction, but with high CVD risk criteria according to the SCORE2/SCORE2 OP. Anthropometric and biochemical parameters were assessed at baseline and after 12 weeks of diet and exercise intervention. Participants were randomly assigned into 3 groups: no intervention group (Group 1a), physical exercise group (Group 1b), and physical exercise (±2 h/week) plus diet group (Group 2). Briefly, the dietary intervention was based on the principles of an isocaloric Mediterranean diet (MD), with seven main meals/week centered on plant-based foods (legumes and pulses). The combined effect of exercise and the diet showed significant decrease in WC ( = 0.002), BST ( < 0.001), visceral fat ( < 0.001), and TG ( = 0.029), compared with control groups. The intervention significantly increased legume intake ( < 0.001), as well as adherence to the MD, which associates with WC decrease ( = 0.024) and visceral fat ( = 0.017). A combined intervention of exercise and diet should be endorsed as an efficient modifier of cardiometabolic parameters.
66Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.PubMed
Guilherme Moura Cunha, German Guzman, Livia Lugarinho Correa De Mello, et al.
Front Endocrinol (Lausanne). 2020 Sep 14;11:607. doi: 10.3389/fendo.2020.00607. eCollection 2020.
Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired -tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at < 0.05. Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group ( < 0.001). Mean reductions in VAT were -32.0 cm for VLCKD group and -12.58 cm for LC group ( < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; < 0.005). Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. ClinicalTrials.gov, identifier: NCT04322110.
67The Effect of a Ketogenic Diet versus Mediterranean Diet on Clinical and Biochemical Markers of Inflammation in Patients with Obesity and Psoriatic Arthritis: A Randomized Crossover Trial.PubMed
Vaia Lambadiari, Pelagia Katsimbri, Aikaterini Kountouri, et al.
Int J Mol Sci. 2024 Feb 20;25(5):2475. doi: 10.3390/ijms25052475.
The effect of different diet patterns on psoriasis (PSO) and psoriatic arthritis (PSA) is unknown. Τhe aim of our study was to evaluate the effectiveness of a Mediterranean diet (MD) and Ketogenic diet (KD), in patients with PSO and PSA. Twenty-six patients were randomly assigned to start either with MD or KD for a period of 8 weeks. After a 6-week washout interval, the two groups were crossed over to the other type of diet for 8 weeks. At the end of this study, MD and KD resulted in significant reduction in weight ( = 0.002, 0.001, respectively), in BMI ( = 0.006, 0.001, respectively), in waist circumference (WC) ( = 0.001, 0.001, respectively), in total fat mass ( = 0.007, 0.001, respectively), and in visceral fat ( = 0.01, 0.001, respectively), in comparison with baseline. After KD, patients displayed a significant reduction in the Psoriasis Area and Severity Index (PASI) ( = 0.04), Disease Activity Index of Psoriatic Arthritis (DAPSA) ( = 0.004), interleukin (IL)-6 ( = 0.047), IL-17 ( = 0.042), and IL-23 ( = 0.037), whereas no significant differences were observed in these markers after MD ( > 0.05), compared to baseline. The 22-week MD-KD diet program in patients with PSO and PSA led to beneficial results in markers of inflammation and disease activity, which were mainly attributed to KD.
68Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.PubMed
Keila Rufatto de Souza, Nicole Alessandra Engel, Hevylin Jacinto Soares, et al.
Metab Brain Dis. 2024 Apr;39(4):635-648. doi: 10.1007/s11011-023-01311-6. Epub 2024 Mar 2.
Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.
69Ramadan intermittent fasting reduces visceral fat and improves gastrointestinal motility.PubMed
Hala Abdallah, Mohamad Khalil, Ilaria Farella, et al.
Eur J Clin Invest. 2023 Sep;53(9):e14029. doi: 10.1111/eci.14029. Epub 2023 May 19.
BACKGROUND: Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility. METHODS: In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis. RESULTS: Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn. CONCLUSIONS: RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.
70Physical activity in management of persons with obesity.PubMed
Jean-Michel Oppert, Alice Bellicha, Cécile Ciangura
Eur J Intern Med. 2021 Nov;93:8-12. doi: 10.1016/j.ejim.2021.04.028. Epub 2021 May 21.
Physical activity and exercise have many benefits in persons with obesity, helping with weight loss, body fat loss, abdominal visceral fat loss and possibly with weight maintenance after weight loss. The effect of exercise training (endurance or endurance plus resistance or high-intensity interval training) alone on weight loss as outcome appears relatively modest, amounting to only a few kg. However, endurance training during weight loss has been shown to increase V̇Omax and resistance training during weight loss leads to lower loss in lean body mass and increased muscle strength. In addition, higher physical activity levels improve cardiovascular risk, whatever weight variations. Specifically, physical activity or exercise is part of lifestyle measures for prevention of type 2 diabetes and substantially helps with metabolic control in patients with type 2 diabetes. The importance of physical activity counselling and exercise prescription in the management strategy will depend on specific treatment objectives as defined for a given patient, including weight loss, prevention of weigh regain, prevention of cardio-metabolic comorbidities, lean body mass preservation but also improvement in quality of life or development of social links. The 5 A's strategy consisting in: Ask, Assess, Advise, Agree, Assist (or Arrange) appears well adapted in this setting. Professionals need to be aware of the many barriers patients with obesity may meet on their way to increase habitual physical activity as specific solutions should be proposed. A major challenge is how to improve adherence to new physical activity habits over time.
71Effect of Exercise Training on Fat Loss-Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution.PubMed
Kristoffer Jensen Kolnes, Maria Houborg Petersen, Teodor Lien-Iversen, et al.
Front Physiol. 2021 Sep 24;12:737709. doi: 10.3389/fphys.2021.737709. eCollection 2021.
In obesity, excessive abdominal fat, especially the accumulation of visceral adipose tissue (VAT), increases the risk of metabolic disorders, such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and non-alcoholic fatty liver disease. Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity. Physical activity is recommended for primary prevention and treatment of obesity, T2DM, and related disorders. Achieving a stable reduction in body weight with exercise training alone has not shown promising effects on a population level. Because fat has a high energy content, a large amount of exercise training is required to achieve weight loss. However, even when there is no weight loss, exercise training is an effective method of improving body composition (increased muscle mass and reduced fat) as well as increasing insulin sensitivity and cardiorespiratory fitness. Compared with traditional low-to-moderate-intensity continuous endurance training, high-intensity interval training (HIIT) and sprint interval training (SIT) are more time-efficient as exercise regimens and produce comparable results in reducing total fat mass, as well as improving cardiorespiratory fitness and insulin sensitivity. During high-intensity exercise, carbohydrates are the main source of energy, whereas, with low-intensity exercise, fat becomes the predominant energy source. These observations imply that HIIT and SIT can reduce fat mass during bouts of exercise despite being associated with lower levels of fat oxidation. In this review, we explore the effects of different types of exercise training on energy expenditure and substrate oxidation during physical activity, and discuss the potential effects of exercise training on adipose tissue function and body fat distribution.
72Aerobic Exercise Prevents High-Fat-Diet-Induced Adipose Tissue Dysfunction in Male Mice.PubMed
Qiaofeng Guo, Nan Li, Haiyan Shi, et al.
Nutrients. 2024 Oct 11;16(20):3451. doi: 10.3390/nu16203451.
BACKGROUND/OBJECTIVES: This study aimed to assess the effect of aerobic exercise on capillary density and vascular smooth muscle cell (VSMC) phenotype in the visceral and subcutaneous adipose tissue of high-fat-diet (HFD) mice in order to understand the mechanisms underlying improvements in insulin resistance (IR) and chronic inflammation in adipose tissue (AT). METHODS: Male C57BL/6J mice were divided into HFD and normal diet groups for 12 weeks and then further split into sedentary and aerobic exercise subgroups for an additional 8 weeks. Various parameters including body weight, fat weight, blood glucose, lipid profile, insulin levels, glucose tolerance, and inflammatory cytokines were evaluated. RESULTS: Aerobic exercise reduced HFD-induced weight gain, IR, and improved lipid profiles. HFD had a minimal effect on inflammatory cytokines except in visceral adipose tissue (VAT). IR was associated with capillary density in subcutaneous adipose tissue (SAT) and VSMC phenotype in VAT. Aerobic exercise promoted anti-inflammatory responses in VAT, correlating with VSMC phenotype in this tissue. CONCLUSIONS: Aerobic exercise can alleviate HFD-induced IR and inflammation through the modulation of VSMC phenotype in AT.
73Exercise and insulin sensitivity: a review.PubMed
L B Borghouts, H A Keizer
Int J Sports Med. 2000 Jan;21(1):1-12. doi: 10.1055/s-2000-8847.
Physical activity has a beneficial effect on insulin sensitivity in normal as well as insulin resistant populations. A distinction should be made between the acute effects of exercise and genuine training effects. Up to two hours after exercise, glucose uptake is in part elevated due to insulin independent mechanisms, probably involving a contraction-induced increase in the amount of GLUT4 associated with the plasma membrane and T-tubules. However, a single bout of exercise can increase insulin sensitivity for at least 16 h post exercise in healthy as well as NIDDM subjects. Recent studies have accordingly shown that acute exercise also enhances insulin stimulated GLUT4 translocation. Increases in muscle GLUT4 protein content contribute to this effect, and in addition it has been hypothesized that the depletion of muscle glycogen stores with exercise plays a role herein. Physical training potentiates the effect of exercise on insulin sensitivity through multiple adaptations in glucose transport and metabolism. In addition, training may elicit favourable changes in lipid metabolism and can bring about improvements in the regulation of hepatic glucose output, which is especially relevant to NIDDM. It is concluded that physical training can be considered to play an important, if not essential role in the treatment and prevention of insulin insensitivity.
74Molecular mechanisms by which aerobic exercise induces insulin sensitivity.PubMed
Habib Yaribeygi, Stephen L Atkin, Luis E Simental-Mendía, et al.
J Cell Physiol. 2019 Aug;234(8):12385-12392. doi: 10.1002/jcp.28066. Epub 2019 Jan 3.
Insulin resistance is a key feature of Type 2 diabetes and an important therapeutic target to address glycemic control to prevent diabetic complications. Lifestyle advice is the first step in the ADA/EASD consensus guidelines followed by metformin therapy. Aerobic exercise (AE) can increase insulin sensitivity by several molecular pathways including upregulation of insulin transporters in the cellular membrane of insulin-dependent cells. In addition, AE improves insulin sensitivity by amelioration of the pathophysiologic pathways involved in insulin resistance such as the reduction of adipokines, inflammatory and oxidative stress responses, and improvement of insulin signal transduction via different molecular pathways. This review details the molecular pathways by which AE induces beneficial effects on insulin resistance.
75Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease.PubMed
Bente Klarlund Pedersen
Eur J Clin Invest. 2017 Aug;47(8):600-611. doi: 10.1111/eci.12781. Epub 2017 Jul 19.
BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact cardiometabolic diseases. RESULTS: Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas TNF-α is a key molecule in peripheral insulin resistance. In addition, TNF-α appears to be involved in the pathogenesis of atherosclerosis and heart failure. A marked increase in IL-6 and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1ra, thereby limiting IL-1β signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance. In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic diseases.
76Role of exercise on visceral adiposity after spinal cord injury: a cardiometabolic risk factor.PubMed
Jacob A Goldsmith, Areej N Ennasr, Gary J Farkas, et al.
Eur J Appl Physiol. 2021 Aug;121(8):2143-2163. doi: 10.1007/s00421-021-04688-3. Epub 2021 Apr 23.
PURPOSE: Visceral adipose tissue (VAT) is associated with cardiometabolic disease risk in able-bodied (AB) populations. However, the underlying mechanisms of VAT-induced disease risk are unknown in persons with spinal cord injury (SCI). Potential mechanisms of VAT-induced cardiometabolic dysfunction in persons with SCI include systemic inflammation, liver adiposity, mitochondrial dysfunction, and anabolic deficiency. Moreover, how exercise interventions impact these mechanisms associated with VAT-induced cardiometabolic dysfunction are still being explored. METHODS: A search for relevant scientific literature about the effects of exercise on VAT and cardiometabolic health was conducted on the PubMed database. Literature from reference lists was also included when appropriate. RESULTS: Both aerobic and resistance exercise training beneficially impact health and VAT mass via improving mitochondrial function, glucose effectiveness, and inflammatory signaling in SCI and AB populations. Specifically, aerobic exercise appears to also modulate cellular senescence in AB populations and animal models, while resistance exercise seems to augment anabolic signaling in persons with SCI. CONCLUSIONS: The current evidence supports regular engagement in exercise to reduce VAT mass and the adverse effects on cardiometabolic health in persons with SCI. Future research is needed to further elucidate the precise mechanisms by which VAT negatively impacts health following SCI. This will likely facilitate the development of rehabilitation protocols that target VAT reduction in persons with SCI.
77Effect of High-Intensity Interval Training on Total, Abdominal and Visceral Fat Mass: A Meta-Analysis.PubMed
Florie Maillard, Bruno Pereira, Nathalie Boisseau
Sports Med. 2018 Feb;48(2):269-288. doi: 10.1007/s40279-017-0807-y.
BACKGROUND: High-intensity interval training (HIIT) is promoted as a time-efficient strategy to improve body composition. OBJECTIVE: The aim of this meta-analysis was to assess the efficacy of HIIT in reducing total, abdominal, and visceral fat mass in normal-weight and overweight/obese adults. METHODS: Electronic databases were searched to identify all related articles on HIIT and fat mass. Stratified analysis was performed using the nature of HIIT (cycling versus running, target intensity), sex and/or body weight, and the methods of measuring body composition. Heterogeneity was also determined RESULTS: A total of 39 studies involving 617 subjects were included (mean age 38.8 years ± 14.4, 52% females). HIIT significantly reduced total (p = 0.003), abdominal (p = 0.007), and visceral (p = 0.018) fat mass, with no differences between the sexes. A comparison showed that running was more effective than cycling in reducing total and visceral fat mass. High-intensity (above 90% peak heart rate) training was more successful in reducing whole body adiposity, while lower intensities had a greater effect on changes in abdominal and visceral fat mass. Our analysis also indicated that only computed tomography scan or magnetic resonance imaging showed significant abdominal and/or visceral fat-mass loss after HIIT interventions. CONCLUSION: HIIT is a time-efficient strategy to decrease fat-mass deposits, including those of abdominal and visceral fat mass. There was some evidence of the greater effectiveness of HIIT running versus cycling, but owing to the wide variety of protocols used and the lack of full details about cycling training, further comparisons need to be made. Large, multicenter, prospective studies are required to establish the best HIIT protocols for reducing fat mass according to subject characteristics.
78Efficacy of Interval Training in Improving Body Composition and Adiposity in Apparently Healthy Adults: An Umbrella Review with Meta-Analysis.PubMed
Eric Tsz-Chun Poon, Hong-Yat Li, Jonathan Peter Little, et al.
Sports Med. 2024 Nov;54(11):2817-2840. doi: 10.1007/s40279-024-02070-9. Epub 2024 Jul 14.
BACKGROUND: Although the efficacy of interval training for improving body composition has been summarized in an increasing number of systematic reviews in recent years, discrepancies in review findings and conclusions have been observed. OBJECTIVE: This study aims to synthesize the available evidence on the efficacy of interval training compared with moderate-intensity continuous training (MICT) and nonexercise control (CON) in reducing body adiposity in apparently healthy adults. METHODS: An umbrella review with meta-analysis was performed. A systematic search was conducted in seven databases (MEDLINE, EMBASE, Cochrane Database, CINAHL, Scopus, SPORTDiscus, and Web of Science) up to October 2023. Systematic reviews with meta-analyses of randomized controlled trials (RCTs) comparing interval training and MICT/CON were included. Literature selection, data extraction, and methodological quality assessment (AMSTAR-2) were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model. Subgroup analyses were conducted based on the type of interval training [high-intensity interval training (HIIT) and sprint interval training (SIT)], intervention duration, body mass index, exercise modality, and volume of HIIT protocols. RESULTS: Sixteen systematic reviews, including 79 RCTs and 2474 unique participants, met the inclusion criteria. Most systematic reviews had a critically low (n = 6) or low (n = 6) AMSTAR-2 score. Interval training demonstrated significantly greater reductions in total body fat percent (BF%) compared with MICT [weighted mean difference (WMD) of - 0.77%; 95% confidence interval (CI) - 1.12 to - 0.32%] and CON (WMD of - 1.50%; 95% CI - 2.40 to - 0.58%). Significant reductions in fat mass, visceral adipose tissue, subcutaneous abdominal fat, and android abdominal fat were also observed following interval training compared to CON. Subgroup analyses indicated that both HIIT and SIT resulted in superior BF% loss than MICT. These benefits appeared to be more prominent in individuals with overweight/obesity and longer duration interventions (≥ 12 weeks), as well as in protocols using cycling as a modality and low-volume HIIT (i.e., < 15 min of high-intensity exercise per session). CONCLUSIONS: This novel umbrella review with large-scale meta-analysis provides an updated synthesis of evidence with implications for physical activity guideline recommendations. The findings support interval training as a viable exercise strategy for reducing adiposity in the general population.
79Effects of a Cycling versus Running HIIT Program on Fat Mass Loss and Gut Microbiota Composition in Men with Overweight/Obesity.PubMed
Annaëlle Couvert, Leslie Goumy, Florie Maillard, et al.
Med Sci Sports Exerc. 2024 May 1;56(5):839-850. doi: 10.1249/MSS.0000000000003376. Epub 2024 Jan 18.
PURPOSE: High-intensity interval training (HIIT) can efficiently decrease total and (intra-)abdominal fat mass (FM); however, the effects of running versus cycling HIIT programs on FM reduction have not been compared yet. In addition, the link between HIIT-induced FM reduction and gut microbiota must be better investigated. The aim of this study was to compare the effects of two 12-wk HIIT isoenergetic programs (cycling vs running) on body composition and fecal microbiota composition in nondieting men with overweight or obesity. METHODS: Sixteen men (age, 54.2 ± 9.6 yr; body mass index, 29.9 ± 2.3 kg·m -2 ) were randomly assigned to the HIIT-BIKE (10 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) or HIIT-RUN (9 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) group (3 times per week). Dual-energy x-ray absorptiometry was used to determine body composition. Preintervention and postintervention fecal microbiota composition was analyzed by 16S rRNA gene sequencing, and diet was controlled. RESULTS: Overall, body weight, and abdominal and visceral FM decreased over time ( P < 0.05). No difference was observed for weight, total body FM, and visceral FM between groups (% change). Conversely, abdominal FM loss was greater in the HIIT-RUN group (-16.1% vs -8.3%; P = 0.050). The α-diversity of gut microbiota did not vary between baseline and intervention end and between groups, but was associated with abdominal FM change ( r = -0.6; P = 0.02). The baseline microbiota profile and composition changes were correlated with total and abdominal/visceral FM losses. CONCLUSIONS: Both cycling and running isoenergetic HIIT programs improved body composition in men with overweight/obesity. Baseline intestinal microbiota composition and its postintervention variations were correlated with FM reduction, strengthening the possible link between these parameters. The mechanisms underlying the greater abdominal FM loss in the HIIT-RUN group require additional investigations.
80Effects of school-based high-intensity interval training on body composition, cardiorespiratory fitness and cardiometabolic markers in adolescent boys with obesity: a randomized controlled trial.PubMed
Cao Meng, Tang Yucheng, Li Shu, et al.
BMC Pediatr. 2022 Mar 1;22(1):112. doi: 10.1186/s12887-021-03079-z.
BACKGROUND: With accumulating evidence suggesting that CVD has its origins in childhood obesity. The purpose of this study was to determine the effect of a real-world school-based high-intensity interval training intervention on body composition, cardiorespiratory fitness and cardiometabolic markers in obese boys aged 10 to 13 years. METHODS: Forty-five adolescent boys with obesity (age = 11.2 ± 0.7 years, BMI = 24.2 ± 1.0 kg/m), were randomized to high-intensity interval training group (HIIT, n = 15), moderate-intensity continuous training group (MICT, n = 15), or a control group (CON, n = 15). The intervention groups performed three weekly exercise sessions over 12 weeks. HIIT group performed two sets of eight bouts of 15 s run at high-intensity [90 ~ 100% maximal aerobic speed (MAS)] separated by eight bouts of 15 s recovery run at low-intensity (50% MAS), MICT group performed 30 min run at moderate intensity (60 ~ 70% MAS) and CON group were instructed to continue their normal behaviors. All participants had indices of body composition, cardiorespiratory fitness (CRF) and cardiometabolic markers measured at baseline and post-intervention. Statistical differences between and within groups were determined by use of two-way analysis of variance (ANOVA) with repeated measures. RESULTS: Following the school-based training program, BMI and body fat mass decreased (BMI: - 1.8 kg/m vs. - 1.2 kg/m, P < 0.01; FM: - 1.6 kg, P < 0.05 vs. -3.7 kg, P < 0.01) in HIIT and MICT group, but there was no significant difference between the two interventions; [Formula: see text] both increased significantly in two intervention groups, and the increment of HIIT group was significantly greater than that of MICT (6.1 mL/kg/min vs. 3.8 mL/kg/min, P < 0.01), Visceral adipose tissue was significant decrease in HIIT group (- 53 g vs. -17 g, P < 0.01) whilst the MICT group experienced a significant decrease in body fat percentage (- 3.1 ± 1.0 kg, P < 0.01), but there were no significant difference between the two interventions. Low-density lipoprotein cholesterol decreased only in HIIT group (- 17.2%, P < 0.05). Significant decrease in the usual index of insulin resistance (HOMA-IR) occurred in HIIT and MICT groups (- 27.3 and - 28.6%, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that high-intensity interval training based on running can be used to improve the physical health of obese adolescents in school. Further investigations involving a larger cohort of participants, taken from different schools, is recommended. TRIAL REGISTRATION: title Effect of High Intensity Interval Training on Obese Children and Adolescents, time 16/12/2017, ID ChiCTR-IOR-17013992 , website http://www.chictr.org.cn.
81Resistance training suppresses intra-abdominal fatty acid synthesis in ovariectomized rats.PubMed
U S Stotzer, M F C Rodrigues, M M Domingos, et al.
Int J Sports Med. 2015 Mar;36(3):226-33. doi: 10.1055/s-0034-1390494. Epub 2014 Nov 21.
Ovarian hormone loss is associated with a shift in fat distribution to intra-abdomin al adipose tissue (intra-AAT) depots and with lipid metabolism disorders, which predisposes individuals to developing insulin resistance. Resistance training (RT) prevents increases in intra-AAT after ovarian hormone loss. However, the molecular mechanisms underlying these changes remain unclear. We investigated the effects of ovariectomy and RT on gene expression related to lipogenesis and fat oxidation in the intra-AAT of ovariectomized rats. Sprague-Dawley rats (n=6/group) were divided into the groups: sham-sedentary, ovariectomized-sedentary, sham-RT and ovariectomized-RT. RT groups performed a 10-week climbing program on a ladder with progressive overload. Intra-AAT was subjected to morphometric and mRNA analysis. Ovariectomized-sedentary group had larger adipocytes and higher expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), hormone-sensitive lipase (HSL) and lower expression of the oxidative carnitinepalmitoyltransferase-I (CPT-1). RT counteracted OVX-induced increases in PPAR-γ and SCD-1 and decreased SREBP-1c. ACC and HSL were downregulated in ovariectomized-RT compared with the ovariectomized-sedentary group. Ovariectomized-RT group had the highest CPT-1 gene expression. Adipocyte size decreased in ovariectomized-RT group. Results suggest that RT reduces intra-AAT adipocyte size in ovariectomized rats by suppressing intra-AAT fatty acid synthesis and enhancing fatty acid β-oxidation.
82Strength training promotes attenuation of fatty liver while improving insulin resistance and inflammatory biomarkers in obese rats induced by high-fat diet.PubMed
S Torezani-Sales, A P L Damiani, A R Madureira, et al.
Braz J Med Biol Res. 2025 Aug 22;58:e14505. doi: 10.1590/1414-431X2025e14505. eCollection 2025.
Obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). Non-pharmacological strategies, such as strength training (ST), have been investigated for their effectiveness in attenuating MASLD. This study evaluated the effects of ST on hepatic fat accumulation in an experimental model of obesity. Thirty-day-old male Wistar rats (∼150 g) were assigned to either a standard diet (SD) or a high-fat diet (HFD). The experimental protocol lasted 26 weeks and was divided into two phases: 1) obesity induction and maintenance (16 weeks) and 2) ST intervention (10 weeks). After the 16th week, HFD-fed rats were further divided into sedentary obese (Ob) and obese trained (ObST) groups. The ST protocol consisted of 4-5 vertical ladder climbs with 60-s intervals, three times per week, using 50-100% of maximal load. Body weight (BW), fat pads, total body fat (BF), adiposity index (AI), and muscle strength were assessed, as were glycemic, lipid, inflammatory, and histological parameters. ST reduced BW, epididymal and visceral fat depots, triglycerides, total cholesterol, glucose, leptin, and tumor necrosis factor (TNF)-α levels while improving insulin resistance. In conclusion, ST significantly attenuated hepatic steatosis in obesity, promoting metabolic and anti-inflammatory benefits. These findings suggest that ST may be an effective therapeutic strategy for MASLD, and further studies are needed to elucidate its molecular mechanisms and clinical applications.
83Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting.PubMed
Debra L Waters, Lina Aguirre, Burke Gurney, et al.
J Gerontol A Biol Sci Med Sci. 2022 Jan 7;77(1):131-139. doi: 10.1093/gerona/glab111.
BACKGROUND: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown. METHODS: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, and knee strength by dynamometry. RESULTS: IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; -41% vs -28% and -23% and VAT: -36% vs -19% and -21%; p = .003 to .01); IMAT and VAT decreased in all groups more than control (between-group p < .001). ISI increased more in COMB than AEX and REX groups (86% vs 50% and 39%; p = .005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p < .05). Knee strength improved more in COMB and REX than AEX group (all p < .05). Changes in IMAT and VAT correlated with PPT (r = -0.28 and -0.39), VO2peak (r = -0.49 and -0.52), gait speed (r = -0.25 and -0.36), and ISI (r = -0.49 and -0.52; all p < .05). CONCLUSIONS: Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity.
84Effects of Tai Chi or Conventional Exercise on Central Obesity in Middle-Aged and Older Adults : A Three-Group Randomized Controlled Trial.PubMed
Parco M Siu, Angus P Yu, Edwin C Chin, et al.
Ann Intern Med. 2021 Aug;174(8):1050-1057. doi: 10.7326/M20-7014. Epub 2021 Jun 1.
BACKGROUND: Central obesity is a major manifestation of metabolic syndrome, which is a common health problem in middle-aged and older adults. OBJECTIVE: To examine the therapeutic efficacy of tai chi for management of central obesity. DESIGN: Randomized, controlled, assessor-blinded trial. (ClinicalTrials.gov: NCT03107741). SETTING: A single research site in Hong Kong between 27 February 2016 and 28 February 2019. PARTICIPANTS: Adults aged 50 years or older with central obesity. INTERVENTION: 543 participants were randomly assigned in a 1:1:1 ratio to a control group with no exercise intervention ( = 181), conventional exercise consisting of aerobic exercise and strength training (EX group) ( = 181), and a tai chi group (TC group) ( = 181). Interventions lasted 12 weeks. MEASUREMENTS: Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity. RESULTS: The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, -4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, -1.8 cm [CI, -2.3 to -1.4 cm]; < 0.001; EX group vs. control: -1.3 cm [CI, -1.8 to -0.9 cm]; < 0.001); both intervention groups also showed reductions in body weight ( < 0.05) and attenuation of the decrease in HDL-C level relative to the control group. The favorable changes in WC and body weight were maintained in both the TC and EX groups, whereas the beneficial effect on HDL-C was only maintained in the TC group at week 38. LIMITATIONS: High attrition and no dietary intervention. CONCLUSION: Tai chi is an effective approach to reduce WC in adults with central obesity aged 50 years or older. PRIMARY FUNDING SOURCE: Health and Medical Research Fund.
85Sleep Duration and Visceral Adipose Tissue: Linear and Nonlinear Mendelian Randomization Analyses.PubMed
Yuefeng Yu, Yingchao Chen, Haojie Zhang, et al.
J Clin Endocrinol Metab. 2022 Nov 23;107(11):2992-2999. doi: 10.1210/clinem/dgac551.
CONTEXT: Increasing evidence suggests that sleep is important for fat metabolism. However, the causal relationship between sleep duration and visceral adipose tissue (VAT) needs to be further clarified. OBJECTIVE: This study investigated the linear and nonlinear causal association between sleep duration and VAT. METHODS: This study used one-sample and two-sample Mendelian randomization MR). Single-nucleotide polymorphisms (SNPs) associated with sleep duration at genome-wide significance were obtained from published genome-wide association studies. We also recalculated the correlation between each SNP and sleep duration in the UK Biobank. The associations of SNPs with predicted VAT (396 858 participants) were conducted in the UK Biobank. RESULTS: A total of 396 858 eligible participants (54.10% females, 57 ± 8 years old) were included in the study. The participants slept 7.17 ± 1.04 hours and stored 1.25 ± 0.88 kg of VAT on average. Genetically predicted sleep duration was significantly associated with VAT. For each 1-hour increase in genetically predicted sleep duration, the reduction in predicted VAT mass was 0.11 kg (P = 8.18E-16) in total, 0.17 kg (P = 3.30E-11) in men and 0.07 kg (P = 1.94E-06) in women. Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and VAT in all participants, men, and women. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the increased VAT. In contrast, no clear evidence on the causal effect of genetically predicted long sleep duration on VAT mass was found. CONCLUSION: The causal association of sleep duration with VAT was L-type. Our findings support that short sleep duration is a risk factor for increasing VAT, thus reinforcing the probability that increasing sleep duration may decrease VAT.
86Chronodisruption enhances inflammatory cytokine release from visceral adipose tissue in obesity.PubMed
Lorenza Zinna, Ludovica Verde, Michele Francesco Di Tolla, et al.
J Transl Med. 2025 Feb 26;23(1):231. doi: 10.1186/s12967-025-06250-7.
BACKGROUND: Chronodisruption, marked by circadian rhythm misalignment, is linked to inflammatory diseases like obesity. Chronotypes, reflecting individual circadian behavior, include morning, intermediate, and evening types, with evening chronotypes showing worse body composition and higher metabolic risk. This study evaluated the inflammatory profile of visceral adipose tissue (VAT) across chronotypes in individuals with obesity and examined clock gene expression. METHODS: Twenty-five participants with obesity (11/14 F/M, BMI 41.59 ± 7.69 kg/m², age 41.13 ± 11.08 years) candidates for bariatric surgery were classified using the Morningness-Eveningness Questionnaire (MEQ): morning (36%), intermediate (28%), or evening (36%) chronotypes. VAT biopsies were analyzed for cytokines, chemokines, and growth factors via multiplex ELISA, and clock genes (PER1, CLOCK, BMAL1) were assessed using qPCR. RESULTS: Body composition and biochemical parameters were similar across groups, but evening chronotypes had higher triglyceride levels (p = 0.012) and lower phase angle (p = 0.035). VAT inflammatory markers, including IL-1β (p = 0.04), IL-8 (p = 0.03), bFGF (p = 0.01), MCP-1 (p = 0.01), and MIP-1β (p = 0.05), were highest in evening and lowest in morning chronotypes. Evening chronotypes had significantly elevated bFGF levels compared to other groups (p = 0.04). PER1 mRNA expression was also higher in evening chronotypes (p = 0.02) and correlated with VAT-released bFGF (p = 0.03) and IL-1β (p = 0.03). MEQ scores negatively correlated with VAT bFGF (p = 0.02), MCP-1 (p = 0.02), and PER1 expressions. CONCLUSION: Despite similar metabolic profiles, evening chronotypes exhibit heightened VAT inflammation and altered clock gene expression, potentially worsening their metabolic risk.
87Habitual nappers and non-nappers differ in circadian rhythms of expression in abdominal adipose tissue explants.PubMed
Carolina Zambrano, Agné Kulyté, Juán Luján, et al.
Front Endocrinol (Lausanne). 2023 Jun 9;14:1166961. doi: 10.3389/fendo.2023.1166961. eCollection 2023.
BACKGROUND AND PURPOSE: Napping is a widespread practice worldwide and has in recent years been linked to increased abdominal adiposity. Lipase E or encodes the protein hormone-sensitive lipase (HSL), an enzyme that plays an important role in lipid mobilization and exhibits a circadian expression rhythm in human adipose tissue. We hypothesized that habitual napping may impact the circadian expression pattern of , which in turn may attenuate lipid mobilization and induce abdominal fat accumulation. METHODS: Abdominal adipose tissue explants from participants with obesity (n = 17) were cultured for a 24-h duration and analyzed every 4 h. Habitual nappers (n = 8) were selected to match non-nappers (n = 9) in age, sex, BMI, adiposity, and metabolic syndrome traits. Circadian expression rhythmicity was analyzed using the cosinor method. RESULTS: Adipose tissue explants exhibited robust circadian rhythms in expression in non-nappers. In contrast, nappers had a flattened rhythm. amplitude was decreased in nappers as compared with non-nappers (71% lower). The decrease in amplitude among nappers was related to the frequency of napping (times per week) where a lower rhythm amplitude was associated with a higher napping frequency (r = -0.80; = 0.018). Confirmatory analyses in the activity of 's protein (i.e., HSL) also showed a significant rhythm in non-nappers, whereas significance in the activity of HSL was lost among nappers. CONCLUSION: Our results suggest that nappers display dysregulated circadian expression as well as dysregulated circadian HSL activity, which may alter lipid mobilization and contribute to increased abdominal obesity in habitual nappers.
88Physical inactivity and breakfast skipping caused visceral fat accumulation in rats.PubMed
Syunsuke Nakajima, Fumiaki Hanzawa, Saiko Ikeda, et al.
Sci Rep. 2024 Sep 30;14(1):22644. doi: 10.1038/s41598-024-68058-7.
Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12-0 in the control group and ZT16-0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society.
89Increase of visceral fat and adrenal gland volume in women with depression: preliminary results of a morphometric MRI study.PubMed
Burkhard Ludescher, Arif Najib, Sophia Baar, et al.
Int J Psychiatry Med. 2008;38(3):229-40. doi: 10.2190/PM.38.3.a.
OBJECTIVE: Depression is often accompanied by increased visceral adipose tissue (VAT), stress, enlarged adrenal glands, and an increased risk of cardiovascular disease. VAT turn-over is regulated by adrenal stress hormones such as cortisol. Aim of this study was to investigate the relationship between the adrenal volume as a marker for long-term stress and the volume fractions of several body fat compartments in healthy and depressive women. METHODS: Ten depressive and 12 healthy women were investigated. Fat compartments (VAT, VAT in the upper abdomen, subcutaneous adipose tissue (SCAT), and adrenal volume) were measured by MRI. RESULTS: Depressive women revealed more VAT in the upper abdomen than the healthy. There was a significant correlation of age and Body Mass Index (BMI) with the visceral adipose tissue volume and adrenal gland size. In a partial correlation, Beck Depression Inventory (BDI) was correlated with VAT in the upper abdomen (r = 0.45, p < 0.05). CONCLUSIONS: The increase of adrenal volume and VAT and the correlation of BDI with VAT in the upper abdomen support the hypothesis of long-term production of stress hormones in depression. This study is a further step toward describing morphologic substrates of depression in endocrine organs.
90Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study.PubMed
Jennifer Daubenmier, Jean Kristeller, Frederick M Hecht, et al.
J Obes. 2011;2011:651936. doi: 10.1155/2011/651936. Epub 2011 Oct 2.
Psychological distress and elevated cortisol secretion promote abdominal fat, a feature of the Metabolic Syndrome. Effects of stress reduction interventions on abdominal fat are unknown. Forty-seven overweight/obese women (mean BMI = 31.2) were randomly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating. We assessed mindfulness, psychological distress, eating behavior, weight, cortisol awakening response (CAR), and abdominal fat (by dual-energy X-ray absorptiometry) pre- and posttreatment. Treatment participants improved in mindfulness, anxiety, and external-based eating compared to control participants. Groups did not differ on average CAR, weight, or abdominal fat over time. However, obese treatment participants showed significant reductions in CAR and maintained body weight, while obese control participants had stable CAR and gained weight. Improvements in mindfulness, chronic stress, and CAR were associated with reductions in abdominal fat. This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR, which may reduce abdominal fat over time.
91Associations of Hair Cortisol Concentrations with General and Organ Fat Measures in Childhood.PubMed
Florianne O L Vehmeijer, Susana Santos, Romy Gaillard, et al.
J Clin Endocrinol Metab. 2021 Jan 23;106(2):e551-e561. doi: 10.1210/clinem/dgaa785.
CONTEXT: Stress may lead to an adverse body fat distribution from childhood onwards. OBJECTIVE: To examine the associations of hair cortisol concentration (HCC) at 6 years with general and organ fat measures, risk of overweight, and nonalcoholic fatty liver disease (NAFLD) at 10 years and to assess whether these were independent of adiposity measures at 6 years. DESIGN, SETTING AND PARTICIPANTS: HCCs were measured in hair of 6-year-old children (n = 2042) participating in the Generation R Study, a population-based prospective cohort study. MAIN OUTCOME MEASURES: Body mass index (BMI), fat mass index measured by dual-energy X-ray absorptiometry scan, and visceral fat index, pericardial fat index, liver fat fraction measured by magnetic resonance imaging and risk of overweight and NAFLD were obtained at 10 years. RESULTS: The associations of higher HCC at 6 years, with higher BMI, fat mass index, and increased risk of overweight at age 10 years are explained by the relationships observed at 6 years. HCCs at 6 years were associated with a higher liver fat fraction (difference 0.11 liver fat fraction standard deviation score; 95% confidence interval [CI] 0.03, 0.18) and a higher risk of NAFLD at 10 years (odds ratio 1.95; 95% CI 1.06, 3.56), independent of fat mass index at 6 years. HCCs were not associated with pericardial or visceral fat indices. CONCLUSIONS: Higher HCCs at 6 years were associated with higher BMI, fat mass index, liver fat fraction, and higher risks of overweight and NAFLD at 10 years. Only the associations for liver fat fraction and NAFLD were independent of fat mass index at 6 years.
92Modifying influence of dietary sugar in the relationship between cortisol and visceral adipose tissue in minority youth.PubMed
Lauren E Gyllenhammer, Marc J Weigensberg, Donna Spruijt-Metz, et al.
Obesity (Silver Spring). 2014 Feb;22(2):474-81. doi: 10.1002/oby.20594. Epub 2013 Sep 20.
OBJECTIVE: Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however, findings in humans are mixed, which may be clarified when diet is considered. DESIGN AND METHODS: Participants included 165 African-American and Latino, overweight adolescents (BMI% 97.2±3.2%, ages 13-18, 67% Latino, 66% female). Body composition was determined by dual energy X-ray absorptiometry, abdominal fat depots [VAT, subcutaneous (SAT)] by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age, and total body fat were a priori covariates. RESULTS: There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (P(interaction) ≤ 0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (ß = 0.031 P < 0.001; ß = 0.026 P < 0.001), with no relationship in low consumers of total or added-sugar. CONCLUSION: Dietary sugar may play an important role in modifying the relationship between cortisol and VAT, such that cortisol is significantly associated with elevated VAT under conditions of high sugar intake.
93Pep19: A Novel Approach for Reducing Visceral Fat and Improving Sleep Quality in Obese Adults-Results From an Early-Stage Clinical Trial.PubMed
Andrea S Heimann, Prachi Singh, Emer S Ferro, et al.
Diabetes Metab Res Rev. 2025 Jul;41(5):e70056. doi: 10.1002/dmrr.70056.
BACKGROUND: Conformational-sensitive antibodies were used to identify the orally active peptide DIIADDEPLT (Pep19) as an inverse agonist of cannabinoid type 1 receptor. Pep19 safely improved metabolic parameters in murine models of diet-induced obesity, and in healthy dogs. OBJECTIVES: To evaluate Pep19's impact on quality of life and body composition in obese adults, hypothesising that the metabolic effects of Pep19 observed in animal models could translate to humans. METHODS: Subjects, males (n = 12) and females (n = 12), from 46 to 59 years old, weighing 91-106 kg, body mass index between 30 and 35 kg/m, were evaluated over 60 days in a placebo-controlled, triple-blinded clinical trial; participants received either a placebo, 2 or 5 mg Pep19 capsules once daily at bedtime. The primary endpoint was a broad measure of quality of life assessed using validated questionnaires. The key secondary endpoints included weight loss, reduction in visceral fat (measured by dual-energy X-ray absorptiometry), and changes in waist, hip, and chest measurements. RESULTS: Pep19 was well tolerated with no reported adverse effects. Remarkable reductions in visceral fat were observed in the 5 mg Pep19 group, with a 17 ± 4.7% loss (p < 0.05), without any change in lean mass. Additionally, sleep quality improved significantly by 35 ± 10% in the 2 mg Pep19 group and 25 ± 16% in the 5 mg Pep19 group (p < 0.05). In the 5 mg Pep19 group, significant reductions in body weight and waist circumferences were also observed (p < 0.05). CONCLUSION: Despite the limitations related to the use of convenience sampling, a small sample size, and a short intervention duration, which may restrict generalisation and health claims, Pep19 demonstrates exceptional innovative potential as a novel approach to reduce visceral fat and improve sleep quality.
94Safety and efficacy of liraglutide on reducing visceral and ectopic fat in adults with or without type 2 diabetes mellitus: A systematic review and meta-analysis.PubMed
Fengling He, Wei Chen, Wenlong Xu, et al.
Diabetes Obes Metab. 2023 Mar;25(3):664-674. doi: 10.1111/dom.14908. Epub 2022 Nov 21.
AIM: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). METHODS: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non-T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. RESULTS: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta-analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = -0.72, 95% confidence interval (CI; -1.12, -0.33)], liver fat [SMD = -0.78, 95% CI (-1.24, -0.32)] and body mass index [weighted mean difference = -1.44, 95% CI (-1.95, -0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = -0.74, 95% CI (-1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. CONCLUSIONS: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured.
95Impact of Visceral and Hepatic Fat on Cardiometabolic Health.PubMed
Tasveer Khawaja, Matthew Nied, Abigail Wilgor, et al.
Curr Cardiol Rep. 2024 Nov;26(11):1297-1307. doi: 10.1007/s11886-024-02127-1. Epub 2024 Sep 5.
PURPOSE OF REVIEW: Body fat distribution plays a significant role in the cardiometabolic consequences of obesity. We review the impact of visceral and hepatic fat and highlight important interventions. RECENT FINDINGS: Several epidemiologic studies have established a clear association between visceral fat and cardiovascular disease. The association between hepatic fat and cardiovascular disease is less clear with discordant results. Novel evidence demonstrates sodium glucose co-transporter-2 (SGLT2) inhibitors facilitate modest weight loss and reductions in ectopic fat depots in patient with type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with decreased visceral/hepatic fat and reductions in MACE in populations with type 2 diabetes and with overweight/obesity. Clear associations between visceral fat and cardiometabolic outcomes have been established, whereas the impact of hepatic fat remains less clear. Lifestyle modification and pharmacologic interventions remain the initial therapies, while surgical intervention is associated with improved long-term outcomes. Emerging therapies have demonstrated a profound impact on body fat distribution and cardiometabolic risk.
96Effects of liraglutide on body composition in people living with obesity or overweight: A systematic review.PubMed
Pedro Henrique Siedschlag Schmidt, Eric Pasqualotto, Henrique Vilar Dos Santos, et al.
Obes Res Clin Pract. 2025 Jan-Feb;19(1):11-18. doi: 10.1016/j.orcp.2025.01.009. Epub 2025 Feb 3.
AIM: To evaluate the effect of liraglutide on body composition in people living with obesity or overweight. METHODS: A systematic search was conducted in PubMed, Embase, and Cochrane Library databases up to June 10, 2024. Randomized controlled trials (RCTs) comparing liraglutide to placebo and reporting body composition outcomes were included. RESULTS: Data from 15 studies involving 960 participants were analyzed. Liraglutide consistently demonstrated significant reductions in total weight, fat mass, and visceral adipose tissue (VAT) compared to placebo across the included studies. VAT reductions ranged from 12.49 % to 23 %, highlighting liraglutide's effectiveness in targeting visceral fat, a key factor in cardiometabolic risk. Fat mass reductions were also substantial and consistent, reinforcing the efficacy of liraglutide in improving overall body composition. In contrast, lean mass outcomes were more variable, with some studies reporting preservation or even gains in lean mass, while others indicated losses. CONCLUSIONS: Liraglutide effectively reduces fat mass and VAT, supporting its use in managing obesity and related cardiometabolic risks. However, the inability to accurately calculate lean and fat mass proportions underscores the need for standardized reporting and availability of individual-level data. Future research should prioritize these elements and include muscle function assessments to better evaluate the clinical impacts of GLP-1 receptor agonists on body composition.
97Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.PubMed
Manjun Deng, Yonghao Wen, JingXin Yan, et al.
BMC Med. 2023 Nov 16;21(1):447. doi: 10.1186/s12916-023-03129-6.
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. RESULTS: Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. CONCLUSIONS: The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.
98GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis.PubMed
Hongle Yan, Chunyi Huang, Xuejun Shen, et al.
Front Endocrinol (Lausanne). 2022 Jul 13;13:923606. doi: 10.3389/fendo.2022.923606. eCollection 2022.
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce glycaemia and weight and improve insulin resistance (IR) different mechanisms. We aim to evaluate and compare the ability of GLP-1 RAs and SGLT-2 inhibitors to ameliorate the IR of nonalcoholic fatty liver disease (NAFLD) patients. DATA SYNTHESIS: Three electronic databases (Medline, Embase, PubMed) were searched from inception until March 2021. We selected randomized controlled trials comparing GLP-1 RAs and SGLT-2 inhibitors with control in adult NAFLD patients with or without T2DM. Network meta-analyses were performed using fixed and random effect models, and the mean difference (MD) with corresponding 95% confidence intervals (CI) were determined. The within-study risk of bias was assessed with the Cochrane collaborative risk assessment tool RoB. RESULTS: 25 studies with 1595 patients were included in this network meta-analysis. Among them, there were 448 patients, in 6 studies, who were not comorbid with T2DM. Following a mean treatment duration of 28.86 weeks, compared with the control group, GLP-1 RAs decreased the HOMA-IR (MD [95%CI]; -1.573[-2.523 to -0.495]), visceral fat (-0.637[-0.992 to -0.284]), weight (-2.394[-4.625 to -0.164]), fasting blood sugar (-0.662[-1.377 to -0.021]) and triglyceride (- 0.610[-1.056 to -0.188]). On the basis of existing studies, SGLT-2 inhibitors showed no statistically significant improvement in the above indicators. Compared with SGLT-2 inhibitors, GLP-1 RAs decreased visceral fat (-0.560[-0.961 to -0.131]) and triglyceride (-0.607[-1.095 to -0.117]) significantly. CONCLUSIONS: GLP-1 RAs effectively improve IR in NAFLD, whereas SGLT-2 inhibitors show no apparent effect. SYSTEMATIC REVIEW REGISTRATION: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021251704.
99Tirzepatide Once Weekly for the Treatment of Obesity.PubMed
Ania M Jastreboff, Louis J Aronne, Nadia N Ahmad, et al.
N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.
BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).
100Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.PubMed
Louis J Aronne, Deborah Bade Horn, Carel W le Roux, et al.
N Engl J Med. 2025 Jul 3;393(1):26-36. doi: 10.1056/NEJMoa2416394. Epub 2025 May 11.
BACKGROUND: Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown. METHODS: In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. The primary end point was the percent change in weight from baseline to week 72. Key secondary end points included weight reductions of at least 10%, 15%, 20%, and 25% and a change in waist circumference from baseline to week 72. RESULTS: A total of 751 participants underwent randomization. The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001). The least-squares mean change in waist circumference was -18.4 cm (95% CI, -19.6 to -17.2) with tirzepatide and -13.0 cm (95% CI, -14.3 to -11.7) with semaglutide (P<0.001). Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%. The most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation. CONCLUSIONS: Among participants with obesity but without diabetes, treatment with tirzepatide was superior to treatment with semaglutide with respect to reduction in body weight and waist circumference at week 72. (Funded by Eli Lilly; SURMOUNT-5 ClinicalTrials.gov number, NCT05822830.).
101Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.PubMed
Patricia J Rodriguez, Brianna M Goodwin Cartwright, Samuel Gratzl, et al.
JAMA Intern Med. 2024 Sep 1;184(9):1056-1064. doi: 10.1001/jamainternmed.2024.2525.
IMPORTANCE: Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. OBJECTIVE: To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024. EXPOSURES: Tirzepatide or semaglutide in formulations labeled for T2D, on or off label. MAIN OUTCOMES AND MEASURES: On-treatment weight change in a propensity score-matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared. RESULTS: Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups. CONCLUSIONS AND RELEVANCE: In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.
102Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.PubMed
Haiqiang Yao, Anqi Zhang, Delong Li, et al.
BMJ. 2024 Jan 29;384:e076410. doi: 10.1136/bmj-2023-076410.
OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.
103Effects of beinaglutide on visceral fat area and gut microbiota in obesity.PubMed
Tianshui Liu, Weizheng Liang, Fanghua Xu, et al.
Eur J Med Res. 2025 Jun 4;30(1):448. doi: 10.1186/s40001-025-02585-5.
BACKGROUND: The gut microbiota plays a substantial role in obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can affect body weight, insulin resistance, and lipid metabolism via combined hypothalamic feeding centre and gastrointestinal tract activity. It also affects the intestinal flora of patients with obesity. We investigated changes in visceral fat and gut microbiota of patients with obesity treated with beinaglutide. METHODS: Thirty-three patients from our hospital with obesity treated with beinaglutide and 20 sex- and age-matched healthy controls were included based on the inclusion and exclusion criteria. Glycolipid metabolism indices, inflammation indices, and hepatic and renal functions were assessed at treatment initiation and 4 and 12 weeks after treatment. Body weight, waist circumference, blood pressure, and body composition (visceral fat area, body fat, body fat percentage, skeletal muscle, and basal metabolic rate) were measured. The Homeostatic Model Assessment of Insulin Resistance index was calculated. Fecal samples were collected from 12 cases. Effects on intestinal flora were assessed by sequencing the V3-V4 region of the 16S rRNA gene. RESULTS: Beinaglutide significantly reduced visceral fat area, improved glycolipid metabolism, and decreased total cholesterol, low-density lipoprotein cholesterol, blood glucose, and C-reactive protein levels. It also considerably restored the α-diversity of intestinal flora, with decreased in relative abundances of Prevotella, Lachnospira and Dialister at the genus level and increased in the relative abundance of Blautia A and Gemmiger A. CONCLUSIONS: Our findings provide insights into the mechanisms by which beinaglutide aids weight loss, particularly via modulating the gut microbiota.
104Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus.PubMed
Chrysi Koliaki, John Doupis
Diabetes Ther. 2011 May;2(2):101-21. doi: 10.1007/s13300-011-0002-3. Epub 2011 Feb 28.
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials.
105The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome.PubMed
Krzysztof Bednarz, Karolina Kowalczyk, Marlena Cwynar, et al.
Int J Mol Sci. 2022 Apr 14;23(8):4334. doi: 10.3390/ijms23084334.
Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.
106Endurance Training Improves GLP-1 Sensitivity and Glucose Tolerance in Overweight Women.PubMed
Thorbjörn Åkerström, Malene N Stolpe, Renate Widmer, et al.
J Endocr Soc. 2022 Jul 26;6(9):bvac111. doi: 10.1210/jendso/bvac111. eCollection 2022 Sep 1.
CONTEXT AND OBJECTIVE: Obesity and inactivity are risk factors for developing impaired glucose tolerance characterized by insulin resistance and reduced beta-cell function. The stimulatory effect of glucagon-like peptide 1 (GLP-1) on insulin secretion is also impaired in obese, inactive individuals. The aim of this study was to investigate whether endurance training influences beta-cell sensitivity to GLP-1. PARTICIPANTS AND INTERVENTION: Twenty-four female participants, age 46 ± 2 years, body mass index 32.4 ± 0.9 kg/m, and maximal oxygen consumption 24.7 ± 0.8 mL/kg/min participated in a 10-week exercise training study. METHODS: Beta-cell sensitivity to GLP-1 was assessed in a subset of participants (n = 6) during a 120-minute hyperglycemic glucose clamp (8.5 mM) including a 1-hour GLP-1 (7-36 amide) infusion (0.4 pmol/kg/min). Changes in glucose tolerance, body composition, and cardiorespiratory fitness were assessed by oral glucose tolerance tests (OGTTs), dual-energy X-ray absorptiometry scans, magnetic resonance scans, and maximal oxygen consumption (VOmax) tests, respectively. RESULTS: The c-peptide response to infusion of GLP-1 increased 28 ± 3% ( < 0.05) toward the end of the hyperglycemic clamp. The insulin response remained unchanged. Training improved glucose tolerance and reduced GLP-1, insulin, and glucagon levels during the OGTTs. Training increased VOmax (from 24.7 ± 0.8 to 27.0 ± 0.7 mL/kg/min; < 0.05) and reduced visceral fat volume (from 4176 ± 265 to 3888 ± 266 cm; < 0.01). CONCLUSION: Along with improved glycemic control, endurance training improved beta-cell sensitivity to GLP-1 in overweight women. The study was deemed not to constitute a clinical trial and was not registered as such.
107Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.PubMed
Louis J Aronne, Naveed Sattar, Deborah B Horn, et al.
JAMA. 2024 Jan 2;331(1):38-48. doi: 10.1001/jama.2023.24945.
IMPORTANCE: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. OBJECTIVE: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. INTERVENTIONS: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. RESULTS: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. CONCLUSIONS AND RELEVANCE: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04660643.
108The Korean traditional medicine Gyeongshingangjeehwan inhibits obesity through the regulation of leptin and PPARalpha action in OLETF rats.PubMed
Sunhyo Jeong, Kyungsil Chae, Yang Sam Jung, et al.
J Ethnopharmacol. 2008 Sep 26;119(2):245-51. doi: 10.1016/j.jep.2008.06.037. Epub 2008 Jul 15.
Gyeongshingangjeehwan (GGEx), which comprises Liriope platyphylla F.T. Wang & T. Tang (Liliaceae), Platycodongrandiflorum A. DC. (Campanulaceae), Schisandrachinensis K. Koch (Magnoliaceae), and Ephedra sinica Stapf (Ephedraceae), has traditionally been used as an anti-obesity drug in Korean local clinics, although there is no evidence concerning the scientific analyses of its effects and mechanism(s) of action. Thus, we investigated the effects of GGEx on obesity, as well as the mechanism by which GGEx functions, in Otsuka Long-Evans Tokushima Fatty (OLETF) male rats. Compared with obese OLETF control rats, administration of GGEx for 8 weeks significantly decreased food intake and plasma leptin levels as well as body weight gain and abdominal fat in OLETF rats. GGEx treatment not only decreased circulating triglycerides, but also inhibited lipid accumulation in the liver. GGEx increased the hepatic mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation. Consistent with the in vivo data, GGEx elevated PPARalpha reporter gene expression in NMu2Li liver cells. These results suggest that GGEx may effectively prevent obesity and hypertriglyceridemia in part through the inhibition of feeding and the activation of hepatic PPARalpha.
109Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde in High Fat Diet Induced Obese Rats.PubMed
Mohammad Rafiul Haque, H Shahid Ansari
Drug Res (Stuttg). 2018 Nov;68(11):637-647. doi: 10.1055/a-0590-1956. Epub 2018 Apr 10.
Arq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.
110Anti-obesity effects of Diospyros lotus leaf extract in mice with high-fat diet-induced obesity.PubMed
Bo-Mi Kim, Byoung Ok Cho, Seon Il Jang
Int J Mol Med. 2019 Jan;43(1):603-613. doi: 10.3892/ijmm.2018.3941. Epub 2018 Oct 18.
Diospyros (D.) lotus has been demonstrated to have antioxidant and anti‑inflammatory properties. The purpose of the present study was to evaluate the effect of D. lotus leaf water extract (DLE) on high‑fat diet (HFD)‑induced obesity in C57BL/6 mice. The present study first investigated the effect of DLE on the lipid accumulation and triglyceride (TG) contents in 3T3‑L1 cells, and the results revealed that treatment with DLE suppressed the lipid accumulation and TG level. Subsequently, the anti‑obesity effects of DLE were investigated in vivo. Oral administration of DLE reduced the body weight gain, food efficiency ratio, and liver and visceral fat weight in mice fed with a HFD. DLE administration in these mice also reduced TG, total cholesterol, low‑density lipoprotein cholesterol, glucose, insulin and leptin levels, as well as the atherogenic index. Furthermore, DLE administration decreased hepatic steatosis, as well as serum aspartate transaminase, alanine transaminase and alkaline phosphatase levels in mice fed with HFD. It was further observed that treatment of the HFD‑fed mice with DLE prevented lipid peroxidation, while it recovered glutathione depletion and the activities of superoxide dismutase, catalase and glutathione peroxidase. In conclusion, the current study suggests that the anti‑obesity effect of DLE may provide positive insights as a potential functional food ingredient for the prevention of obesity.
111[The impact of phenolic compounds on pig fat deposition].PubMed
Yaxin Wang, Xuekai Tian, Gongshe Yang, et al.
Sheng Wu Gong Cheng Xue Bao. 2024 May 25;40(5):1486-1497. doi: 10.13345/j.cjb.230498.
The quantity and distribution of fat deposits are crucial factors that impact the quality of pork. Recent studies have indicated that the utilization of natural ingredients plays a significant role in decreasing subcutaneous and visceral fat deposits, as well as enhancing intramuscular fat. Moreover, natural products possess several advantages including being environmentally friendly, safe, free of additives, and leaving no residue. Phenolic compounds derived from fruits, vegetables and herbs constitute of vital component of these natural ingredients. This article examines the influence of phenolic compounds on pig fat deposition, aiming to provide guidance on the utilization of such compounds to regulate fat deposition and enhance pork quality.
112The problem of obesity: is there a role for antagonists of the renin-angiotensin system?PubMed
Richard S Weisinger, Denovan P Begg, Nora Chen, et al.
Asia Pac J Clin Nutr. 2007;16 Suppl 1:359-67.
Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin II (ANG II) is the biologically active component of the renin-angiotensin system (RAS). The RAS is present in adipose tissue and evidence suggests that ANG II is intimately linked to obesity. Indeed, ANG II increases fat cell growth and differentiation, increases synthesis, uptake and storage of fatty acids and triglycerides and possibly inhibits lipolysis. Evidence obtained using genetically modified animals has shown that the amount of body fat is directly related to the amount of ANG II, i.e., animals with low levels of ANG II have reduced fat stores while animals with excessive ANG II have increased fat stores. In humans, epidemiological evidence has shown that body fat is correlated with angiotensinogen, a precursor of ANG II, or other components of the RAS. Furthermore, blocking the production and/or actions of ANG II with drugs or natural substances decreases body fat. The decrease in body fat caused by such treatments predominantly occurs in abdominal fat depots and appears to be independent of energy intake and digestibility. Clearly, ANG II has an important role in the accumulation of body fat and the possibility exists that treatment of obesity will be enhanced by the use of natural or synthetic substances that interfere with ANG II.
113Visceral obesity and the metabolic syndrome: effects of weight loss.PubMed
L Busetto
Nutr Metab Cardiovasc Dis. 2001 Jun;11(3):195-204.
A large body of experimental and epidemiological evidence has established an association between visceral obesity and the metabolic syndrome, which retains its power throughout the spectrum of adiposity and is still clinically meaningful in severe obesity. The association may be due to an overload of liver free fatty acids (FFA) produced by the high lipolytic activity of omental fat. A substantial improvement in all aspects of the metabolic syndrome with only a moderate degree of weight loss has been observed in a large number of randomised controlled studies and can also be obtained in severe obesity, despite the fact that the patients remain obese. The reasons for this apparent dissociation between weight loss and metabolic improvement are not yet clearly understood, but may involve the relationship between visceral fat and metabolic alterations. The results of some studies suggest that the favourable metabolic changes observed in obese patients with weight loss may be directly attributable to a reduction in visceral fat, and other studies have recently shown that a rapid and preferential reduction in visceral fat mass occurs during the first phase of weight loss in morbidly obese patients possibly as a result of sympathetic nervous system activation. It is therefore possible that the apparent dissociation between weight loss and metabolic improvement is partially due to a difference in the responsiveness of visceral and subcutaneous adipose tissue to energy restriction: i.e. the fact that the metabolic profile of patients with visceral obesity may substantially improve after the loss of only a few kilograms of body weight could be related to a greater relative reduction in the amount of visceral rather than other fat. In this respect, the characteristically high rate of visceral fat mobilisation can also be seen as a good target for interventions aimed at reducing cardiovascular risk factors.
114Effect of liraglutide on ectopic fat in polycystic ovary syndrome: A randomized clinical trial.PubMed
Signe Frøssing, Malin Nylander, Elizaveta Chabanova, et al.
Diabetes Obes Metab. 2018 Jan;20(1):215-218. doi: 10.1111/dom.13053. Epub 2017 Aug 11.
Women with polycystic ovary syndrome (PCOS) were treated with the GLP-1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled, randomized clinical trial 72 women with PCOS, with a BMI > 25 kg/m and/or insulin resistance, were treated with liraglutide or received placebo 1.8 mg/d (2:1) for 26 weeks. Liver fat content was assessed by HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds (all P < .01). Sex-hormone-binding-globulin (SHBG) levels increased by 19% (P = .03), and free testosterone decreased by 19% (P = .054). HbA1c, fasting glucose and leptin were reduced (all: P < .05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26 weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.
115Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial.PubMed
Ian J Neeland, Steven P Marso, Colby R Ayers, et al.
Lancet Diabetes Endocrinol. 2021 Sep;9(9):595-605. doi: 10.1016/S2213-8587(21)00179-0. Epub 2021 Aug 3.
BACKGROUND: Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. METHODS: In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m or BMI of at least 27 kg/m with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620. FINDINGS: Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo). INTERPRETATION: In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes. FUNDING: NovoNordisk.
116Cardiometabolic Effects of Anti-obesity Pharmacotherapy.PubMed
Andrew R Crawford, Naji Alamuddin, Anastassia Amaro
Curr Atheroscler Rep. 2018 Mar 6;20(4):18. doi: 10.1007/s11883-018-0719-9.
PURPOSE OF REVIEW: We review recent studies discussing the impact of pharmacologic agents for weight loss on clinical cardiovascular events, as well as cardiometabolic risk factors. RECENT FINDINGS: Pharmacotherapy with current FDA-approved medications for weight loss can significantly improve known risk factors for the development of cardiovascular disease such as hypertension, hyperlipidemia, insulin resistance, inflammatory biomarkers, and the quantity of visceral fat, as well as non-alcoholic fatty liver disease. However, data regarding the actual reduction in clinical cardiovascular events with the use of weight loss medications is scarce. Pharmacotherapy for weight loss may have additional benefit in optimizing patient's cardiometabolic comorbidities and improving their clinical cardiovascular outcomes, but each drug should be carefully selected based upon individual patient characteristics.
117The Efficacy of an Energy-Restricted Anti-Inflammatory Diet for the Management of Obesity in Younger Adults.PubMed
Gordana Kenđel Jovanović, Ines Mrakovcic-Sutic, Sandra Pavičić Žeželj, et al.
Nutrients. 2020 Nov 22;12(11):3583. doi: 10.3390/nu12113583.
There is growing evidence of the dietary impact on obesity-induced low-grade chronic inflammation and the associated chronic non-communicable diseases modification. We determined changes in body composition and cardiometabolic and inflammatory status of participants with obesity after 24 weeks of a dietary intervention based on an energy-reduced anti-inflammatory diet and examined the relationship of these changes with changes in the inflammatory potential of the diet. The anthropometric and body composition parameters of 81 participants (average age of 43 years, 74 women) were assessed. Metabolic status was determined using the glycemic and lipid statuses, and the cardiometabolic index and inflammatory status were determined using the concentration of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). The inflammatory potential of the diet was assessed using the Dietary Inflammatory Index (DII). Intervention with an anti-inflammatory diet resulted in a significant reduction in body weight and visceral adipose tissue and caused improvements in the participants' cardiometabolic and inflammatory statuses. The anti-inflammatory diet was shown to be effective regarding obesity management. The study data could advance current scientific knowledge in the field of inflammation and diet, provide guidelines for obesity management, and find its application in routine clinical practice.
118Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.PubMed
Kimber L Stanhope, Jean Marc Schwarz, Nancy L Keim, et al.
J Clin Invest. 2009 May;119(5):1322-34. doi: 10.1172/JCI37385. Epub 2009 Apr 20.
Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.
119Body Composition and Metabolic Improvement in Patients Followed Up by a Multidisciplinary Team for Obesity in China.PubMed
Difei Lu, Zhenfang Yuan, Lihua Yang, et al.
J Diabetes Res. 2021 Jul 29;2021:8862217. doi: 10.1155/2021/8862217. eCollection 2021.
BACKGROUND: This study evaluated the effectiveness of the multidisciplinary team (including a specialist, a dietitian, a physical exercise trainer, a surgeon for bariatric surgery, an acupuncturist, and several health educators) for obesity management and the body composition change and improvements in metabolic biomarkers during a 2-year follow-up. MATERIALS AND METHODS: A total of 119 patients participated in the multidisciplinary team for obesity. Patients were followed up at 3 months, 6 months, 1 year, 18 months, and 2 years after their first visit. Individuals were divided into the high-protein diet (HPD) and standard-protein diet (SPD) group according to their results on a diet questionnaire that they filled out during follow-up. RESULTS: After 1.2 years, the mean body weight of the participants dropped from 89.7 kg to 80.9 kg ( < 0.001). The body adiposity index was reduced from 33.9 to 32.0 ( < 0.001), while the fat-free mass index from 17.0 to 15.2 ( = 0.043). Fasting glucose and HbA1c were also lower after treatment ( = 0.002 and 0.038 for FPG and HbA1c, respectively). Fasting insulin and HOMA-IR were reduced ( = 0.002 and <0.001 for fasting insulin and HOMA-IR, respectively). HDL-c increased along with weight loss (1.06 mmol/L vs. 1.19 mmol/L, < 0.001), and transaminase levels significantly dropped ( = 0.001 and 0.021 for ALT and AST, respectively). During treatment, mean protein intake was 29.9% in the HPD group and 19.5% in the SPD group ( < 0.001). Weight loss, reduction of visceral fat area, maintenance of lean body mass, body adiposity index, and fat-free mass index showed no statistical significance between the HPD and SPD groups, as well as glucose metabolic variables. CONCLUSIONS: A multidisciplinary team for obesity management could significantly reduce body weight and improve metabolic indicators, including HDL-c, transaminase, and insulin resistance. A high-protein diet does not produce better weight control or body composition compared with a standard calorie-restricted diet.
120Lifestyle intervention is more effective in high 1-hour post-load glucose than in prediabetes for restoring β-cell function, reducing ectopic fat, and preventing type 2 diabetes.PubMed
Yiying Wang, Arvid Sandforth, Reiner Jumprtz-von Schwartzenberg, et al.
Metabolism. 2026 Jan;174:156430. doi: 10.1016/j.metabol.2025.156430. Epub 2025 Nov 3.
BACKGROUND: High 1-h-post-load plasma glucose (1 h-PG) is an early diabetes risk marker. We hypothesized that isolated high 1 h-PG represents an intermediate state between normal glucose regulation (NGR) and impaired glucose regulation (IGR) and is amendable to greater lifestyle intervention (LI) benefit. METHODS: In the Tübingen Lifestyle Intervention Program, 317 people with either NGR, IGR or isolated high 1 h-PG without IGR underwent LI for 9 months to achieve ≥5 % weight loss. RESULTS: Before LI initiation, insulin sensitivity and β-cell function declined progressively from NGR (n = 106) to high 1 h-PG (n = 96) and to IGR (n = 115). Visceral adipose tissue (VAT) volume and liver fat content increased from NGT to high 1 h-PG and to IGR. LI improved insulin sensitivity and ß-cell function in the high 1 h-PG group to levels observed in NGR together with a marked reduction in hepatic fat content. Compared to the IGR group, T2D risk was reduced by 80 % (37-96 %, p = 0.005) in the high 1 h-PG group during a 12-year follow-up period. The odds of remission to complete normoglycemia were doubled in the high 1 h-PG group compared to the IGR group (2.18 [1.13-4.28], p = 0.021). CONCLUSION: High 1 h-PG indicates an intermediate metabolic state with pathophysiological changes more severe than in NGR but milder than in IGR. In people with high 1 h-PG, LI significantly improved insulin sensitivity and β-cell function and reduced ectopic lipid deposition and the risk of developing T2D compared to IGR. These findings highlight the value of 1 h-PG as a clinically useful biomarker, providing a critical window for early intervention to reverse core metabolic defects driving prediabetes and T2D.
121Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk.PubMed
Richard N Bergman, Stella P Kim, Isabel R Hsu, et al.
Am J Med. 2007 Feb;120(2 Suppl 1):S3-8; discussion S29-32. doi: 10.1016/j.amjmed.2006.11.012.
Visceral adiposity has been identified as an independent risk factor for cardiovascular disease and the so-called metabolic syndrome. The canine obesity model closely recapitulates the correlation between human visceral adiposity and insulin resistance. A recent canine study indicates that insulin expands the volume of distribution associated with skeletal muscle, and that its ability to enhance macromolecular distribution within this space is blunted in the fat-fed obese canine model. Our canine study supports the portal theory of insulin resistance, in which free fatty acids (FFAs) from visceral fat directly enter the liver and have a detrimental effect on insulin action. The role of adipokines in this condition remains less clear. Sympathetic nervous system hyperactivity in obesity may also contribute to excessive FFA release, hypertension, and insulin resistance. Pathologies interrelated with insulin resistance include beta-cell hypersecretion, reduced insulin clearance, and resultant hyperinsulinemia. An observed nocturnal increase in plasma FFA levels may account for both insulin resistance and compensatory hyperinsulinemia and warrants further investigation. The elucidation of these interrelated pathologies may help reveal points where medical intervention can reduce metabolic disease.
122Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults: A Randomized Clinical Trial.PubMed
Hana Kahleova, Kitt Falk Petersen, Gerald I Shulman, et al.
JAMA Netw Open. 2020 Nov 2;3(11):e2025454. doi: 10.1001/jamanetworkopen.2020.25454.
IMPORTANCE: Excess body weight and insulin resistance lead to type 2 diabetes and other major health problems. There is an urgent need for dietary interventions to address these conditions. OBJECTIVE: To measure the effects of a low-fat vegan diet on body weight, insulin resistance, postprandial metabolism, and intramyocellular and hepatocellular lipid levels in overweight adults. DESIGN, SETTING, AND PARTICIPANTS: This 16-week randomized clinical trial was conducted between January 2017 and February 2019 in Washington, DC. Of 3115 people who responded to flyers in medical offices and newspaper and radio advertisements, 244 met the participation criteria (age 25 to 75 years; body mass index of 28 to 40) after having been screened by telephone. INTERVENTIONS: Participants were randomized in a 1:1 ratio. The intervention group (n = 122) was asked to follow a low-fat vegan diet and the control group (n = 122) to make no diet changes for 16 weeks. MAIN OUTCOMES AND MEASURES: At weeks 0 and 16, body weight was assessed using a calibrated scale. Body composition and visceral fat were measured by dual x-ray absorptiometry. Insulin resistance was assessed with the homeostasis model assessment index and the predicted insulin sensitivity index (PREDIM). Thermic effect of food was measured by indirect calorimetry over 3 hours after a standard liquid breakfast (720 kcal). In a subset of participants (n = 44), hepatocellular and intramyocellular lipids were quantified by proton magnetic resonance spectroscopy. Repeated measure analysis of variance was used for statistical analysis. RESULTS: Among the 244 participants in the study, 211 (87%) were female, 117 (48%) were White, and the mean (SD) age was 54.4 (11.6) years. Over the 16 weeks, body weight decreased in the intervention group by 5.9 kg (95% CI, 5.0-6.7 kg; P < .001). Thermic effect of food increased in the intervention group by 14.1% (95% CI, 6.5-20.4; P < .001). The homeostasis model assessment index decreased (-1.3; 95% CI, -2.2 to -0.3; P < .001) and PREDIM increased (0.9; 95% CI, 0.5-1.2; P < .001) in the intervention group. Hepatocellular lipid levels decreased in the intervention group by 34.4%, from a mean (SD) of 3.2% (2.9%) to 2.4% (2.2%) (P = .002), and intramyocellular lipid levels decreased by 10.4%, from a mean (SD) of 1.6 (1.1) to 1.5 (1.0) (P = .03). None of these variables changed significantly in the control group over the 16 weeks. The change in PREDIM correlated negatively with the change in body weight (r = -0.43; P < .001). Changes in hepatocellular and intramyocellular lipid levels correlated with changes in insulin resistance (both r = 0.51; P = .01). CONCLUSIONS AND RELEVANCE: A low-fat plant-based dietary intervention reduces body weight by reducing energy intake and increasing postprandial metabolism. The changes are associated with reductions in hepatocellular and intramyocellular fat and increased insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02939638.
123Assessment of obesity in chronic kidney disease: what is the best measure?PubMed
Carmine Zoccali, Claudia Torino, Giovanni Tripepi, et al.
Curr Opin Nephrol Hypertens. 2012 Nov;21(6):641-6. doi: 10.1097/MNH.0b013e328358a02b.
PURPOSE OF REVIEW: Obesity is a major driver of the current epidemic of chronic kidney disease (CKD), but metrics of obesity in the CKD population have been studied sparsely. This review updates knowledge on this issue. RECENT FINDINGS: Measures of abdominal obesity, waist circumference and waist-to-hip ratio (WHR), are better predictors than BMI of the high risk of mortality in predialysis and dialysis patients and waist circumference reliably reflects visceral fat in CKD patients. Skinfold thickness and WHR are superior to BMI for the classification of obesity in CKD patients. Multifrequency body impedance analysis (BIA) provides valid estimates of fat mass in hemodialysis patients. SUMMARY: Skinfold thickness,WHR and multifrequency BIA are superior to BMI for measuring body fat in CKD patients and measures of abdominal obesity are stronger predictors of adverse clinical outcomes than the BMI. These metrics should be preferentially applied for the assessment of obesity in CKD, but it remains unproven that these techniques offer real advantages over the BMI in clinical practice in CKD patients.
124Self-reported waist circumference compared with the 'Waist Watcher' tape-measure to identify individuals at increased health risk through intra-abdominal fat accumulation.PubMed
T S Han, M E Lean
Br J Nutr. 1998 Jul;80(1):81-8. doi: 10.1017/s0007114598001809.
We evaluated the accuracy of self-reported home-assessed and self-measured waist circumference in 101 men and eighty-three women aged 28-67 years. The main outcome measures were subjects' self-reported and self-measured waist circumference, and self-classification according to the previously defined waist action level 1 (940 mm in men, 800 mm in women) and action level 2 (1020 mm in men, 880 mm in women), and waist circumference measured by the investigator using the 'Waist Watcher' tape-measure, as the reference method. The mean errors (95% CI limits of agreement) for subjects' self-reported waist circumference (self-reported minus reference; mm) were -67 (95% CI -210, 77) in men and -43 (95% CI -211, 123) in women, and for self-measured waist circumference (mm) using the 'Waist Watcher' (self-measured minus reference) were -5 (95% CI -62, 52) in men and -4 (95% CI -50, 42) in women. The proportions of subjects classified into waist action level 1 or action level 2 by the investigator were used as the reference method. Self-reported waist circumference of men and women respectively would be classified correctly in different categories based on action level 1 with sensitivities of 58.3 and 78.7%, and specificities of 92.5 and 91.7%, and action level 2 with sensitivities of 35.3 and 44.9%, and specificities of 98.5 and 90.7%. Using the 'Waist Watcher' with different colour bands based on the action levels, male and female subjects respectively classified themselves into correct categories according to action level 1 with sensitivities of 100 and 95.7%, and specificities of 95.1 and 97.2%, and according to action level 2 with sensitivities of 97.1 and 100%, and specificities of 100% for both sexes. Only 2% of the sample misclassified themselves into the wrong categories according to waist circumference action levels. In conclusion, people tend to underestimate their waist circumference, but the 'Waist Watcher' tape-measure offers advantages over self-reported home-assessed measurement, and may be used as a screening tool for self-classifying the risk of ill health through intra-abdominal fat accumulation.
125Assessment of correlation between conventional anthropometric and imaging-derived measures of body fat composition: a systematic literature review and meta-analysis of observational studies.PubMed
Sofia Mouchti, Josefina Orliacq, Gillian Reeves, et al.
BMC Med Imaging. 2023 Sep 14;23(1):127. doi: 10.1186/s12880-023-01063-w.
BACKGROUND: In studies of the association of adiposity with disease risk, widely used anthropometric measures of adiposity (e.g. body-mass-index [BMI], waist circumference [WC], waist-hip ratio [WHR]) are simple and inexpensive to implement at scale. In contrast, imaging-based techniques (e.g. magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA]) are expensive and labour intensive, but can provide more accurate quantification of body fat composition. There is, however, limited evidence about the relationship between conventional and imaging-derived measures of adiposity. METHODS: We searched Scopus and Web of Science for published reports in English of conventional versus imaging-derived measurements of adiposity. We identified 42 articles (MRI = 22; DXA = 20) that met selection criteria, involving 42,556 (MRI = 15,130; DXA = 27,426) individuals recruited from community or hospital settings. Study-specific correlation coefficients (r) were transformed using Fisher's Z transformation, and meta-analysed to yield weighted average correlations, both overall and by ancestry, sex and age, where feasible. Publication bias was investigated using funnel plots and Egger's test. RESULTS: Overall, 98% of participants were 18 + years old, 85% male and 95% White. BMI and WC were most strongly correlated with imaging-derived total abdominal (MRI-derived: r = 0.88-; DXA-derived: 0.50-0.86) and subcutaneous abdominal fat (MRI-derived: 0.83-0.85), but were less strongly correlated with visceral abdominal fat (MRI-derived: 0.76-0.79; DXA-derived: 0.80) and with DXA-derived %body fat (0.76). WHR was, at best, strongly correlated with imaging-derived total abdominal (MRI-derived: 0.60; DXA-derived: 0.13), and visceral abdominal fat (MRI-derived: 0.67; DXA-derived: 0.65), and moderately with subcutaneous abdominal (MRI-derived: 0.54), and with DXA-derived %body fat (0.58). All conventional adiposity measures were at best moderately correlated with hepatic fat (MRI-derived: 0.36-0.43). In general, correlations were stronger in women than in men, in Whites than in non-Whites, and in those aged 18 + years. CONCLUSIONS: In this meta-analysis, BMI and WC, but not WHR, were very strongly correlated with imaging-derived total and subcutaneous abdominal fat. By comparison, all three measures were moderately or strongly correlated with imaging-based visceral abdominal fat, with WC showing the greatest correlation. No anthropometric measure was substantially correlated with hepatic fat. Further larger studies are needed to compare these measures within the same study population, and to assess their relevance for disease risks in diverse populations.
126Quantification of hepatic and visceral fat by CT and MR imaging: relevance to the obesity epidemic, metabolic syndrome and NAFLD.PubMed
Peter M Graffy, Perry J Pickhardt
Br J Radiol. 2016 Jun;89(1062):20151024. doi: 10.1259/bjr.20151024. Epub 2016 Mar 9.
Trends in obesity have continued to increase in the developed world over the past few decades, along with related conditions such as metabolic syndrome, which is strongly associated with this epidemic. Novel and innovative methods to assess relevant obesity-related biomarkers are needed to determine the clinical significance, allow for surveillance and intervene if appropriate. Aggregations of specific types of fat, specifically hepatic and visceral adiposity, are now known to be correlated with these conditions, and there are a variety of imaging techniques to identify and quantify their distributions and provide diagnostic information. These methods are particularly salient for metabolic syndrome, which is related to both hepatic and visceral adiposity but currently not defined by it. Simpler non-specific fat measurements, such as body weight, abdominal circumference and body mass index are more frequently used but lack the ability to characterize fat location. In addition, non-alcoholic fatty liver disease (NAFLD) is a related condition that carries relevance not only for obesity-related diseases but also for the progression of the liver-specific disease, including non-alcoholic steatohepatitis and cirrhosis, albeit at a much lower frequency. Recent CT and MRI techniques have emerged to potentially optimize diagnosing metabolic syndrome and NAFLD through non-invasive quantification of visceral fat and hepatic steatosis with high accuracy. These imaging modalities should aid us in further understanding the relationship of hepatic and visceral fat to the obesity-related conditions such as metabolic syndrome, NAFLD and cardiovascular disease.
127Techniques for the measurement of visceral fat: a practical guide.PubMed
K van der Kooy, J C Seidell
Int J Obes Relat Metab Disord. 1993 Apr;17(4):187-96.
The measurement of fat distribution has become an important issue in obesity research. Numerous techniques have been developed to assess visceral fat because this fat seems to be most strongly associated with metabolic disorders. This review focuses on methods for the direct and indirect assessment of visceral fat ranging from multiple-scan computerized tomography to anthropometric measurements. The principles of techniques, their accuracy and reproducibility as well as aspects of costs and safety are discussed. Comparison of the different methods shows that imaging techniques, such as computerized tomography and magnetic resonance imaging, are the optimal techniques available for accurate assessment of visceral fat. Methods other than imaging techniques have limited potential in the measurement of changes in visceral fat deposition. Anthropometric measurements can be useful to classify subjects into different types of fat distribution for diagnosis of abdominal obesity, and for general application in epidemiological studies. The choice of a particular technique should be based on a balance of practical and financial considerations and the aim of the study. Involvement of ionizing radiation exposure may be an important element in the decision-making process.
128Comparison between DXA and MRI for the Visceral Fat Assessment in Athletes.PubMed
Hiroko Murata, Tomoyoshi Yagi, Taishi Midorikawa, et al.
Int J Sports Med. 2022 Jun;43(7):625-631. doi: 10.1055/a-1717-1619. Epub 2022 Feb 2.
The use of dual-energy X-ray absorptiometry (DXA) may be invalid for assessing athletes with larger bodies, larger lean body mass, and thicker trunks. This study compared the athletes' visceral adipose tissue (VAT) assessed using DXA and magnetic resonance imaging (MRI). Eighty-two Japanese male collegiate athletes from 18 sports participated in this study. VAT was assessed using the dual-energy scan that coincided with the 4th lumbar vertebra. The sum of eight magnetic resonance slices corresponding to the region of the dual-energy scan was used for comparison. The VAT volume was higher with the dual-energy scan than with MRI (difference: 35 cm, p<0.01). A significant correlation was noted between the volumes measured using both modalities (r=0.88, p<0.01). Magnetic resonance-derived volumes less than 600 cm showed a stronger significant correlation with dual-energy-derived volumes. However, magnetic resonance-derived VAT volumes exceeding 600 cm were not significantly correlated with dual-energy-derived volumes. In conclusion, VAT volumes derived from DXA were larger and significantly correlated with those derived from MRI across a wide range of values. Methods using DXA for assessing the visceral fat volume may require adjustment to estimate abdominal visceral fat volume in athletes, with care taken when using such methods for heavyweight athletes.
129Deep learning-based quantification of abdominal fat on magnetic resonance images.PubMed
Andrew T Grainger, Nicholas J Tustison, Kun Qing, et al.
PLoS One. 2018 Sep 20;13(9):e0204071. doi: 10.1371/journal.pone.0204071. eCollection 2018.
Obesity is increasingly prevalent and associated with increased risk of developing type 2 diabetes, cardiovascular diseases, and cancer. Magnetic resonance imaging (MRI) is an accurate method for determination of body fat volume and distribution. However, quantifying body fat from numerous MRI slices is tedious and time-consuming. Here we developed a deep learning-based method for measuring visceral and subcutaneous fat in the abdominal region of mice. Congenic mice only differ from C57BL/6 (B6) Apoe knockout (Apoe-/-) mice in chromosome 9 that is replaced by C3H/HeJ genome. Male congenic mice had lighter body weight than B6-Apoe-/- mice after being fed 14 weeks of Western diet. Axial and coronal T1-weighted sequencing at 1-mm-thickness and 1-mm-gap was acquired with a 7T Bruker ClinScan scanner. A deep learning approach was developed for segmenting visceral and subcutaneous fat based on the U-net architecture made publicly available through the open-source ANTsRNet library-a growing repository of well-known neural networks. The volumes of subcutaneous and visceral fat measured through our approach were highly comparable with those from manual measurements. The Dice score, root-mean-square error (RMSE), and correlation analysis demonstrated the similarity between two methods in quantifying visceral and subcutaneous fat. Analysis with the automated method showed significant reductions in volumes of visceral and subcutaneous fat but not non-fat tissues in congenic mice compared to B6 mice. These results demonstrate the accuracy of deep learning in quantification of abdominal fat and its significance in determining body weight.
130Measurement of visceral fat and abdominal obesity by single-frequency bioelectrical impedance and CT: a cross-sectional study.PubMed
Zhengyang Xu, Yandong Liu, Chengxi Yan, et al.
BMJ Open. 2021 Oct 11;11(10):e048221. doi: 10.1136/bmjopen-2020-048221.
OBJECTIVES: The measurement of visceral fat (VF) is clinically important for the identification of individuals at high risk of visceral obesity-related health conditions. Bioelectrical impedance analysis (BIA) is a widely available and frequently used body composition assessment method, but there have been few validation studies for the measurement of VF. This validation study investigated agreement between BIA and CT for the assessment of VF in adults. DESIGN: Cross-sectional study. SETTING: Between 2015 and 2016 in China. PARTICIPANTS: A total of 414 adults (119 men and 295 women) aged 40-82 years. PRIMARY AND SECONDARY OUTCOME MEASURES: CT-visceral fat area (VFA) was derived at the L2-3 and umbilicus level and VFA cut-offs for visceral obesity applied. BIA measurements of visceral fat level were compared with CT VFA findings using scatter plots and receiver operator characteristic (ROC) curves. RESULTS: Scatter plots showed poor agreement between BIA and CT-derived visceral fat measurements in both sexes (R=0.387-0.636). ROC curves gave optimum figures for sensitivity and specificity of 65% and 69% in women and 76% and 70% in men, respectively, for BIA to discriminate between adults with normal levels of VF and those with visceral obesity determined by CT. CONCLUSION: BIA has limited accuracy for the assessment of VF in adults in practice when compared with the criterion method.
131Sagittal abdominal diameter: A novel and potentially superior indicator than waist circumference for diagnosis of central obesity, based on evidence from multiple data sources.PubMed
Zhuoqing Hu, Rutao Liang, Yimei Chen, et al.
Atherosclerosis. 2025 Mar;402:119107. doi: 10.1016/j.atherosclerosis.2025.119107. Epub 2025 Jan 25.
BACKGROUND AND AIMS: Our previous research reported a visceral fat area (VFA) estimation equation primarily based on sagittal abdominal diameter (SAD), demonstrating favorable performance compared to traditional Waist Circumference (WC)-based equations. While WC is widely used for central obesity measurement, its accuracy needs improvement. This study aims to investigate whether SAD has advantages over WC in diagnosing central obesity and to determine the optimal cut-off values for diagnosis. METHODS: This cross-sectional, retrospective cohort study analyzed 6762 individuals from NHANES (2011-2016) and 701 from Chinese health examinations (2023). ROC curve analysis compared AUC of different indicators in identifying two or more non-adipose components of Metabolic Syndrome (MetS). RESULTS: SAD exhibited the strongest correlation with VFA and demonstrated the strongest associations with most metabolic parameters compared to WC and BMI. Furthermore, compared with WC, SAD had significantly higher AUC values in diagnosing two or more non-adipose components of MetS, with the difference being significant in the NHANES database population (all p < 0.001). The optimal SAD cut-off value was approximately 21.0 cm for both genders and populations, with MetS prevalence increasing rapidly at SAD≥22.0 cm. Subgroup analysis of NHANES revealed variations in optimal SAD cut-off values: Other Races (23.7 cm), Non-Hispanic Black females (18.8 cm), and other subgroups (20.0-22.0 cm). CONCLUSION: SAD demonstrates higher efficacy than WC in diagnosing central obesity, suggesting its suitability for assessing central obesity. Additionally, SAD shows potential for a unified diagnostic cut-off value across genders and regions.
132Physical activity and exercise for weight loss and maintenance in people living with obesity.PubMed
Jean-Michel Oppert, Cécile Ciangura, Alice Bellicha
Rev Endocr Metab Disord. 2023 Oct;24(5):937-949. doi: 10.1007/s11154-023-09805-5. Epub 2023 May 5.
Physical activity and exercise training programs are integral part of a comprehensive obesity management approach. In persons with overweight or obesity, exercise training, specifically aerobic (i.e. endurance) training, is associated with significant additional weight loss compared to the absence of training. However the magnitude of effect remains modest amounting to only 2-3 kg additional weight loss on average. Comparable effects have been observed for total fat loss. Exercise training, specifically aerobic training, is also associated with decreased abdominal visceral fat as assessed by imaging techniques, which is likely to benefit cardiometabolic health in persons with obesity. Based on data from controlled trials with randomization after prior weight loss, the evidence for weight maintenance with exercise training is as yet not conclusive, although retrospective analyses point to the value of relatively high-volume exercise in this regard. Resistance (i.e. muscle-strengthening) training is specifically advised for lean mass preservation during weight loss. Given the relatively limited effect of exercise training on weight loss as such, the changes in physical fitness brought about by exercise training cannot be overlooked as they provide major health benefits to persons with obesity. Aerobic, as well as combined aerobic and resistance training, increase cardiorespiratory fitness (VO) while resistance training, but not aerobic training, improves muscle strength even in the absence of a significant change in muscle mass. Regarding the overall management strategy, adherence in the long term to new lifestyle habits remains a challenging issue to be addressed by further research.
133The effectiveness of social-support-based weight-loss interventions-a systematic review and meta-analysis.PubMed
Mette Tækker Jensen, Svetlana Solgaard Nielsen, Christina Jessen-Winge, et al.
Int J Obes (Lond). 2024 May;48(5):599-611. doi: 10.1038/s41366-024-01468-9. Epub 2024 Feb 8.
OBJECTIVE: This systematic review and meta-analysis examined the effectiveness of social-support-based weight-loss interventions in adult populations with excess weight or obesity. METHODS: We performed a systematic review of randomized controlled trials that reported on the effectiveness of weight-loss interventions which incorporated a social connectedness component. To this end, we conducted a rigorous database search of MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and PubMed for relevant articles. The quality of eligible trials was evaluated by the Cochrane Risk-of-Bias2 tool. Five meta-analyses on intervention effectiveness in terms of weight loss were executed at 2-4-month assessment, 6-month assessment, end of intervention, and 3- and 6-month follow-up. RESULTS: Twenty-four trials involving couples or peers targeting weight loss in 4 919 adults with BMI ≥ 25 met inclusion criteria. Meta-analyses detected no significant effect of social-support-based weight-loss interventions at either 2-4 month or 6-month assessment. There were, however, significant effects at end of intervention [95% CI 0.39, p = 0.04] and at 3-month [95% CI 0.63, p < 0.01] and 6-month [95% CI 0.34, p = 0.05] follow-up. CONCLUSIONS: There seem to be a significant effect at the end of intervention and 3- and 6-month follow-up. However, further high-quality studies are needed before drawing any clear conclusions. TRIAL REGISTRATION: PROSPERO 2020 CRD42020173696.
134A high adherence level to nutritional recommendations minimizes protein and minerals loss while maximizes visceral fat loss in bariatric surgery patients.PubMed
Hadil Subih, Shirin Batayneh, Belal Obeidat, et al.
Surg Obes Relat Dis. 2025 Mar;21(3):301-310. doi: 10.1016/j.soard.2024.10.011. Epub 2024 Oct 12.
BACKGROUND: Metabolic bariatric surgeries are considered the finest and most appropriate treatment option for patients with severe obesity. Besides the surgical procedure, many factors appear to be associated with improved postoperative outcomes such as compliance to the postoperative diet and supplementation, regular physical activity, medical and nutritional follow-up, and modifications in dietary habits. OBJECTIVES: The objectives of this study were to investigate the effect of adherence to postoperative recommendations on anthropometric measurements and body composition and assess the percentage of total weight loss (%TWL) and excess weight loss (%EWL) 3 months postoperative. SETTINGS: Fifty-two participants who underwent a Roux-en-Y gastric bypass or sleeve gastrectomy in the University of Jordan Hospital were included. METHODS: Participants have filled out a preoperative questionnaire. Anthropometric measurements were obtained preoperative and 3 months postoperative using a Body Impedance Analyzer (Inbody 270). The adherence to postoperative recommendations was assessed by the Bariatric Surgery Self-management Questionnaire 3 months postoperative and classified to 3 adherence levels. RESULTS: Most anthropometric measurements decreased 3 months postoperative in the 3 adherence groups (P ≤ .05). No significant differences were observed between groups in anthropometric measurements and body composition, except for minerals and visceral fat levels. The mineral loss has decreased in both the high and intermediate adherence groups (-.09 ± .22 kg, and -.09 ± .18 kg, respectively). Also, the high adherence group showed less loss in protein amount postoperatively (P = .06). Visceral fat level decreased in the high adherence group (P ≤ .05). CONCLUSIONS: Adherence to postoperative behavioral and nutritional recommendations was associated with less protein and mineral loss and enhanced visceral fat reduction postoperatively.
135Effect of a Nurse-Led Diabetes Self-Management Education Program on Glycosylated Hemoglobin among Adults with Type 2 Diabetes.PubMed
Golnaz Azami, Kim Lam Soh, Shariff Ghazali Sazlina, et al.
J Diabetes Res. 2018 Jul 8;2018:4930157. doi: 10.1155/2018/4930157. eCollection 2018.
In recent years, great emphasis has been placed on the role of nonpharmacological self-management in the care of patients with diabetes. Studies have reported that nurses, compared to other healthcare professionals, are more likely to promote preventive healthcare seeking behaviors. The aim of this study was to investigate the effectiveness of a nurse-led diabetes self-management education on glycosylated hemoglobin. A two-arm parallel-group randomized controlled trial with the blinded outcome assessors was designed. One hundred forty-two adults with type 2 diabetes were randomized to receive either usual diabetes care (control group) or usual care plus a nurse-led diabetes self-management education (intervention group). Duration of the intervention was 12 weeks. The primary outcome was glycosylated hemoglobin (HbA1c values). Secondary outcomes were changes in blood pressure, body weight, lipid profiles, self-efficacy (efficacy expectation and outcome expectation), self-management behaviors, quality of life, social support, and depression. Outcome measures were assessed at baseline and at 12-week and 24-week postrandomizations. Patients in the intervention group showed significant improvement in HbA1c, blood pressure, body weight, efficacy expectation, outcome expectation, and diabetes self-management behaviors. The beneficial effect of a nurse-led intervention continued to accrue beyond the end of the trial resulting in sustained improvements in clinical, lifestyle, and psychosocial outcomes. This trial is registered with IRCT2016062528627N1.
136Autonomy support, self-regulation, and weight loss.PubMed
Amy A Gorin, Theodore A Powers, Richard Koestner, et al.
Health Psychol. 2014 Apr;33(4):332-9. doi: 10.1037/a0032586. Epub 2013 Jun 3.
OBJECTIVE: Social support is believed to contribute to weight loss success, yet the type of support received is rarely assessed. To develop more effective weight loss interventions, examinations of the types of support that are associated with positive outcomes are needed. Self-Determination Theory suggests that support for an individual's autonomy is beneficial and facilitates internalization of autonomous self-regulation. We examined whether autonomy support and directive forms of support were associated with weight loss outcomes in a larger randomized controlled trial. METHOD: Adults (N = 201; 48.9 ± 10.5 years; 78.1% women) participating in a weight loss trial were assessed at 0, 6, and 18 months. Autonomy support (AS), directive support, and autonomous self-regulation (ASR) were measured at 0 and 6 months and examined in relation to 18-month weight loss outcomes. RESULTS: Baseline AS and ASR did not predict outcomes; however, AS and ASR at 6 months positively predicted 18-month weight losses (ps < .05), encouragement of healthy eating at 6 months was negatively related to 18-month weight losses (p < .01), and other forms of directive support were not associated with outcomes. CONCLUSIONS: Autonomy support predicted better weight loss outcomes while some forms of directive support hindered progress. Weight loss trials are needed to determine whether family members and friends can be trained to provide autonomy support and whether this is more effective than programs targeting more general or directive forms of support.
137Concurrent Changes in Diet Quality and Physical Activity and Association With Adiposity in Adults.PubMed
Shayan Aryannezhad, Fumiaki Imamura, Emanuella De Lucia Rolfe, et al.
JAMA Netw Open. 2025 Nov 3;8(11):e2545232. doi: 10.1001/jamanetworkopen.2025.45232.
IMPORTANCE: Diet and physical activity (PA) are both associated with body weight, but less is understood about how long-term changes in these behaviors may be associated with changes in adiposity in the general population. OBJECTIVE: To evaluate associations of concurrent changes in diet quality and PA with different body composition indices. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among participants in the UK population-based Fenland study, with repeated measurements of health behaviors and adiposity. Data collection occurred in 2005 to 2015 and 2014 to 2020, with a mean (SD) follow-up of 7.2 (2.0) years. Data were analyzed from January 2024 through April 2025. EXPOSURES: Mediterranean diet score (MDS), a measure of adherence to the Mediterranean diet (range, 0-15 points), was assessed with a food frequency questionnaire. PA energy expenditure (PAEE), measured in kilojoules per kilogram per day, was assessed and calibrated with heart rate and movement sensing. Change variables were derived. MAIN OUTCOMES AND MEASURES: Indices of total adiposity (weight, body mass index and body fat) and regional adiposity (waist circumference, visceral adipose tissue [VAT], and subcutaneous adipose tissue) were assessed with anthropometry and dual-energy x-ray absorptiometry. Hepatic steatosis was ascertained by abdominal ultrasonography. RESULTS: The analysis included 7256 participants (mean [SD; range] age at recruitment, 48.8 [7.4; 29-65] years; 3748 female [51.7%]). In multivariable linear regression models after adjustment for potential confounders and baseline values, changes in both exposures were negatively associated with changes in all adiposity indices. For example, each 1-SD (1.27 points) increase in the change in MDS was negatively associated with changes in adiposity measures (change in body fat: β = -0.47 kg; 95% CI, -0.58 to -0.36 kg; change in VAT: β = -45 g; 95% CI, -55 to -35 g), and each 1-SD (19.0 kJ/kg/d) in the change in PAEE was similarly negatively associated with changes in adiposity measures (change in body fat: β = -1.40 kg; 95% CI, -1.51 to -1.26 kg; change in VAT: β = -108 g; 95% CI, -118 to -98 g) . Despite no evidence for a diet-PA interaction, simultaneous increases in MDS and PAEE were associated with a greater magnitude of decrease in adiposity, with a β of -149 g (95% CI, -187 to -111 g) for change in VAT among participants in higher joint change in MDS and change in PAEE tertiles. Associations had higher β values among individuals with overweight or obesity or who were physically inactive at baseline; for example, for each 1-SD increase in the change in PAEE, the β for change in body fat was -0.96 kg (95% CI, -1.10 to -0.81 kg) when baseline BMI was less than 25 and -1.74 kg (95% CI, -1.91 to -1.57 kg) when baseline BMI was 25 or greater (P for interaction < .001). CONCLUSIONS AND RELEVANCE: In this study, improved diet quality and increased PA were independently associated with weight loss or less weight gain and a healthier adiposity profile. Combining these health behaviors was associated with the greatest adiposity-related benefits.
138Do we need anti-obesity drugs?PubMed
Vojtěch Hainer, Irena Aldhoon Hainerová
Diabetes Metab Res Rev. 2012 Dec;28 Suppl 2:8-20. doi: 10.1002/dmrr.2349.
The increasing global prevalence of obesity urgently requires an implementation of efficient preventive and therapeutic measures. Weight loss and its maintenance should be considered one of the most important strategies to reduce the incidence of obesity-related co-morbidities such as diabetes and cardiovascular diseases. Lifestyle modification focused on diet and physical activity represents the essential component of any kind of weight management. However, only an intensive lifestyle intervention can be efficient in terms of long-term weight loss. Anti-obesity drugs affect different targets in the central nervous system or peripheral tissues and improve regulatory and metabolic disturbances that contribute to the development of obesity. Anti-obesity medications provide modest additional fat loss to that achieved by lifestyle modification alone, reduce visceral fat stores, improve programme adherence, weight loss maintenance, diminish obesity-related health risks and improve a quality of life. Anti-obesity drugs do play a role in weight management. Their replacement with placebo is followed by weight regain. Due to adverse events, several anti-obesity drugs were withdrawn from the market over the past few years and currently only orlistat remains available for long-term obesity management. Drug withdrawals, failure of clinical trials with several new anti-obesity compounds as well as inappropriate demands of drug regulating agencies concerning the study protocol led to scepticism about the perspectives in the pharmacotherapy of obesity. However, recently developed anti-obesity medications such as gut hormone analogues and drug combinations provided encouraging results in terms of weight loss, safety and improvement of cardio-metabolic health risks.