运动减轻骨骼肌、肝和胰岛的瘦素抵抗来防治肥胖和2型糖尿病

Exercise Alleviates Leptin Resistance in Skeletal Muscle,Liver and Pancreatic Islet to Prevent Obesity and Type 2 Diabetes

肥胖和2型糖尿病存在时,瘦素调控外周代谢组织或器官例如骨骼肌、肝、胰岛等的糖脂代谢的作用得不到充分发挥,出现外周瘦素抵抗。减轻外周瘦素抵抗对于防治肥胖及2型糖尿病具有重要意义。运动改善肥胖和2型糖尿病糖脂代谢紊乱等的作用与运动减轻外周瘦素抵抗有关。运动除了调控瘦素信号通路下游因子信号转导,及转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白质酪氨酸磷酸酶1 B(protein tyrosine phosphatase 1B,PTP1B)、细胞因子信号转导抑制因子3(suppressor of cytokine signaling 3,SOCS3)和降低内质网应激来减轻肥胖和2型糖尿病骨骼肌、肝、胰岛的瘦素抵抗外,还通过增加肌肉质量和脂肪酸氧化、减少甘油三酯沉积来减轻外周瘦素抵抗。此外,最新研究发现,血管生成素样蛋白6(angiopoietin-like protein 6,ANGPTL6)和肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)参与运动改善肝和胰岛的瘦素抵抗。本文在简述瘦素外周效应和外周瘦素抵抗的基础上,主要综述了运动减轻肥胖和2型糖尿病外周瘦素抵抗,包括骨骼肌、肝和胰岛瘦素抵抗的作用机制新认识,以期为运动减轻肥胖和防治2型糖尿病的机制研究提供新视角。

In obesity and type 2 diabetes,the effects of leptin on regulating glucose and lipid metabolism are diminished in peripheral tissues or organs such as skeletal muscle,liver and pancreatic islet,implying the development of peripheral leptin resistance.Reducing peripheral leptin resistance is important for the treatment of obesity and type 2 diabetes.Notably,the essential role of exercise in management of glucose and lipid metabolism disorders in obesity and type 2 diabetes has been associated with decreased peripheral leptin resistance.In addition to regulating the downstream factors including signal transducer and activator of transcription 3(STAT3),protein tyrosine phosphatase 1B(PTP1B)and suppressor of cytokine signaling 3(SOCS3)of leptin signaling and inhibiting endoplasmic reticulum stress to attenuate leptin resistance of skeletal muscle,liver and pancreatic islet in obesity and type 2 diabetes,exercise also reduces peripheral leptin resistance by increasing muscle mass and fatty acid oxidation as well as reducing triglyceride accumulation.Besides,recent studies have revealed that angiopoietin-like protein 6(ANGPTL6)and tumor necrosis factorα(TNF-α)participate in exercise-mediated decrease of leptin resistance in liver and pancreatic islet.This review mainly summarized the mechanisms of exercise-induced improvements of leptin resistance in skeletal muscle,liver and pancreatic islet after giving a brief introduction to leptin’s actions and peripheral leptin resistance,which could shed some light on the mechanisms of exercise improving obesity and type 2 diabetes.