Nephrology Division, Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406 Ferrol, Spain.
Medical School, Santiago de Compostela University, Santiago de Compostela, Spain.
Curr Diabetes Rev. 2024;20(5):e160823219824. doi: 10.2174/1573399820666230816111624.
The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance.
肥胖的代谢和心血管并发症风险是由体脂肪分布而非总体脂肪量决定的。与皮下脂肪不同，内脏脂肪（包括肝脂肪变性）反映胰岛素抵抗，并可预测 2 型糖尿病和心血管疾病。在人类中，现有证据表明，在皮下脂肪组织中储存甘油三酯的能力反映了胰岛素敏感性的增强。前瞻性研究表明，基线时较大的皮下脂肪量与糖耐量受损发生率降低之间存在相关性。病例对照研究揭示了胰岛素抵抗的遗传易感性与皮下脂肪组织量减少之间的相关性。人类过氧化物酶体增殖物激活受体γ（PPAR-γ）促进皮下脂肪细胞分化和皮下脂肪沉积，改善胰岛素抵抗并减少内脏脂肪。噻唑烷二酮类药物再现了 PPAR-γ 激活的作用，因此增加了皮下脂肪量，同时增强了胰岛素敏感性并减少了内脏脂肪。部分或几乎完全缺乏脂肪组织（脂肪营养不良）与胰岛素抵抗及其临床表现有关，包括原发性高血压、高三酰甘油血症、高密度脂蛋白胆固醇降低、2 型糖尿病、心血管疾病和肾脏疾病。普拉德-威利综合征患者表现出严重的皮下肥胖而没有胰岛素抵抗。在皮下脂肪组织中积累脂肪的能力受损可能是由于甘油三酯合成不足、脂滴形成不足或脂肪细胞分化缺陷所致。瘦人和肥胖人在皮下脂肪组织储存脂肪的能力耗尽且无法再在该部位沉积甘油三酯时，会发展为胰岛素抵抗。现有的脂肪细胞变大，反映出存在胰岛素抵抗。
