Peng Weihui, Jin Zhangliu, Liu Jinjin, Zhang Qirui, Liu Wei
Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Biliopancreatic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
J Food Sci. 2025 Apr;90(4):e70171. doi: 10.1111/1750-3841.70171.
Obesity, characterized by excessive body fat, is a leading preventable cause of death globally and represents one of the most critical public health challenges of the 21st century. This study aimed to investigate the action of tangeretin on gut microbiota metabolism and inflammation in high-fat diet (HFD)-induced obese mice. A model of obesity was established using 6-week-old male C57BL/6J mice fed with HFD, which were then used for the treatment with tangeretin (20 mg/kg/mice/day) or antibiotic (Abx). The results showed that the tangeretin intervention alleviated fat deposition and disorder of cellular structural integrity in the model group. The obese mice showed a significant increase in the levels of lipid (glycerol, triglyceride, and total cholesterol), inflammatory factors (IL-6 and TNF-α), and F4/80 expression in both serum and adipose tissues. Following tangeretin treatment, the levels of lipid, inflammatory factors, and the ratio of F4/80 + CD206 + macrophages were decreased in both serum and adipose tissue. 16S rRNA sequencing and LC-MS/MS analysis revealed that tangeretin decreased obesity in HFD-induced obese mice by interacting with gut microbiota, particularly influencing Parabacteroides, Blautia, and Parasutterella, and amino acids such as threonine, isoleucine, leucine, phenylalanine, arginine, glutamine, L-tryptophan, and tyrosine. Abx-mediated clearance of gut microbiota blocked the HFD-induced obesity and abrogated the therapeutic effects of tangeretin in obese mice. Fecal microbiota transplantation (FMT) proved that clearing gut microbiota with Abx blocked the beneficial effects of FMT intervention. These findings suggested that tangeretin improved HFD-induced obesity by regulating lipid metabolism and modulating F4/80 macrophage activation via gut microbiota.
肥胖症以体内脂肪过多为特征，是全球主要的可预防死因之一，也是21世纪最严峻的公共卫生挑战之一。本研究旨在探讨橘皮素对高脂饮食（HFD）诱导的肥胖小鼠肠道微生物群代谢和炎症的作用。使用6周龄雄性C57BL/6J小鼠喂食HFD建立肥胖模型，然后用橘皮素（20mg/kg/小鼠/天）或抗生素（Abx）进行治疗。结果表明，橘皮素干预减轻了模型组的脂肪沉积和细胞结构完整性紊乱。肥胖小鼠血清和脂肪组织中的脂质（甘油、甘油三酯和总胆固醇）、炎症因子（IL-6和TNF-α）水平以及F4/80表达均显著增加。橘皮素治疗后，血清和脂肪组织中的脂质、炎症因子水平以及F4/80+CD206+巨噬细胞比例均降低。16S rRNA测序和LC-MS/MS分析表明，橘皮素通过与肠道微生物群相互作用降低HFD诱导的肥胖小鼠的肥胖程度，尤其影响副拟杆菌属、布劳特氏菌属和副萨特氏菌属，以及苏氨酸、异亮氨酸、亮氨酸、苯丙氨酸、精氨酸、谷氨酰胺、L-色氨酸和酪氨酸等氨基酸。Abx介导的肠道微生物群清除阻断了HFD诱导的肥胖，并消除了橘皮素对肥胖小鼠的治疗作用。粪便微生物群移植（FMT）证明，用Abx清除肠道微生物群阻断了FMT干预的有益效果。这些发现表明，橘皮素通过调节脂质代谢和通过肠道微生物群调节F4/80巨噬细胞激活来改善HFD诱导的肥胖。
