Ahmed Altayeb, Cule Madeleine, Naz Afreen, Thanaj Marjola, Sorokin Elena P, Odoemelam Chiemela S, Whitcher Brandon, Sattar Naveed, Bell Jimmy D, Thomas E Louise, Yaghootkar Hanieh
School of Natural Sciences, University of Lincoln, Lincoln, UK.
Calico Life Sciences LLC, South San Francisco, California, USA.
J Obes. 2025 Aug 31;2025:7792701. doi: 10.1155/jobe/7792701. eCollection 2025.
To investigate the genetic determinants of fat distribution across anatomical sites and their implications for health outcomes. We analyzed neck-to-knee MRI data from the UK Biobank ( = 37,589) to measure fat at various locations and used Mendelian randomization to assess effects on 26 obesity-related diseases and 94 biomarkers from FinnGen and other consortia. We identified genetic loci associated with 10 fat depots: abdominal subcutaneous adipose tissue ( = 2 loci), thigh subcutaneous adipose tissue (25), thigh intermuscular adipose tissue (15), visceral adipose tissue (7), liver proton density fat fraction (PDFF) (8), pancreas PDFF (11), paraspinal adipose tissue (9), pelvic bone marrow fat (28), thigh bone marrow fat (27), and vertebrae bone marrow fat (5). Genetically higher abdominal subcutaneous adipose tissue was associated with an adverse metabolic profile and higher risks of Type 2 diabetes, and cardiovascular outcomes. Conversely, higher thigh subcutaneous adipose tissue was associated with a favorable profile and lower risks of Type 2 diabetes and cardiovascular outcomes. Higher visceral adipose tissue was associated with gallstones; higher liver PDFF was associated with elevated tyrosine levels, higher Type 2 diabetes risk, and fatty liver disease; pancreas PDFF was associated with thrombotic events; and thigh bone marrow fat was associated with osteoporosis. These results further suggest a unique contribution of fat deposition in different anatomical locations to disease risk, emphasizing the potential, beyond weight loss per se, for future research into depot-specific therapeutic strategies.
为了研究不同解剖部位脂肪分布的遗传决定因素及其对健康结果的影响。我们分析了英国生物银行（n = 37,589）的颈至膝部MRI数据，以测量不同部位的脂肪，并使用孟德尔随机化方法评估对来自芬兰基因库和其他联盟的26种肥胖相关疾病和94种生物标志物的影响。我们确定了与10个脂肪储存部位相关的基因位点：腹部皮下脂肪组织（n = 2个位点）、大腿皮下脂肪组织（25个）、大腿肌间脂肪组织（15个）、内脏脂肪组织（7个）、肝脏质子密度脂肪分数（PDFF）（8个）、胰腺PDFF（11个）、椎旁脂肪组织（9个）、盆腔骨髓脂肪（28个）、大腿骨髓脂肪（27个）和椎骨骨髓脂肪（5个）。遗传上较高的腹部皮下脂肪组织与不良的代谢状况以及2型糖尿病和心血管疾病的较高风险相关。相反，较高的大腿皮下脂肪组织与良好的状况以及2型糖尿病和心血管疾病的较低风险相关。较高的内脏脂肪组织与胆结石相关；较高的肝脏PDFF与酪氨酸水平升高、2型糖尿病风险增加和脂肪肝疾病相关；胰腺PDFF与血栓形成事件相关；大腿骨髓脂肪与骨质疏松症相关。这些结果进一步表明不同解剖部位的脂肪沉积对疾病风险有独特的影响，强调了除了减肥本身之外，未来针对特定储存部位治疗策略研究的潜力。
