Vague之后八十年：对异位脂肪与代谢功能障碍认识的进展。

文献信息

中文摘要

背景： 脂肪组织的分布是肥胖相关疾病风险的关键决定因素。当皮下脂肪组织安全储存能量的能力被超过时，脂质会溢出至内脏脂肪库，增加游离脂肪酸通量，促进胰岛素抵抗，并触发慢性低度炎症。80多年前，医生Jean Vague认识到男性型（中心性）肥胖与心血管代谢疾病之间的关联；随后影像技术的进步扩展了这一框架，将非脂肪器官内的异位脂肪积累纳入其中。肝脏、胰腺、心脏、肾脏、骨骼肌和上气道中的异位脂肪沉积通过脂毒性、脂肪因子失调、氧化应激和局部炎症信号等机制导致器官特异性功能障碍。本综述总结了内脏和异位脂肪与代谢功能障碍相关脂肪性肝病和脂肪性肝炎、2型糖尿病、心血管和肾脏疾病、肌少症性肥胖以及阻塞性睡眠呼吸暂停相关的证据。重要的是，内脏和异位脂肪库是可改变的。生活方式诱导的能量负平衡、基于肠促胰岛素的药物治疗和代谢减重手术可减少内脏和异位脂肪，并改善血糖控制、肝脏脂肪含量、心血管危险因素、身体功能和睡眠呼吸障碍。将异位脂肪特征纳入临床实践可能增强风险分层，并支持对肥胖表型进行更个性化的管理。

英文摘要

The distribution of adipose tissue is a key determinant of obesity-related disease risk. When the capacity of subcutaneous adipose tissue to safely store energy is exceeded, lipid overflow into visceral depots occurs, increasing free fatty acid flux, promoting insulin resistance, and triggering chronic low-grade inflammation. More than 80 years ago, the physician Jean Vague recognized the association between android (central) obesity and cardiometabolic disease; subsequent advances from imaging technologies have expanded this framework to include ectopic fat accumulation within non-adipose organs. Ectopic fat deposition in the liver, pancreas, heart, kidneys, skeletal muscle, and upper airway contributes to organ-specific dysfunction through mechanisms including lipotoxicity, adipokine dysregulation, oxidative stress, and local inflammatory signaling. This review summarizes the evidence linking visceral and ectopic fat to metabolic dysfunction-associated steatotic liver disease and steatohepatitis, type 2 diabetes, cardiovascular and renal disease, sarcopenic obesity, and obstructive sleep apnea. Importantly, visceral and ectopic fat depots are modifiable. Lifestyle-induced energy deficit, incretin-based pharmacotherapy, and metabolic bariatric surgery reduce visceral and ectopic fat and improve glycemic control, liver fat content, cardiovascular risk factors, physical function, and sleep-disordered breathing. Incorporating ectopic fat characterization into clinical practice may enhance risk stratification and support more personalized management of obesity phenotypes.