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脂质代谢中间产物调节骨骼肌胰岛素敏感性

白丹丹, 肖卫华^*

上海体育学院上海市运动与代谢健康前沿科学研究基地，“运动健身科技”省部共建教育部重点实验室，上海 200438

摘要

骨骼肌是人体最大的器官，完成胰岛素刺激下葡萄糖摄取量的80%~90%，与胰岛素抵抗(insulin resistance, IR)的发生、发展密切相关。骨骼肌是脂质代谢的主要场所之一，脂质代谢产物可作为信号分子参与骨骼肌内物质代谢的调控。脂肪酸作为脂质代谢中的产物，可通过胰岛素信号转导、炎症反应和线粒体功能等多种途径来调节骨骼肌胰岛素敏感性。例如：饱和脂肪酸(saturated fatty acids, SFAs)损害胰岛素信号转导、诱发线粒体功能障碍和炎症反应，从而诱导IR；而不饱和脂肪酸则通过增强胰岛素信号转导和发挥抗炎作用逆转SFAs带来的不良影响，从而减轻IR。此外，骨骼肌内脂质代谢紊乱可使有害的代谢中间产物如二酰甘油(diacylglycerol, DAG)、神经酰胺及长链脂酰辅酶A (long-chain acyl-coenzyme A, LCA-CoA)蓄积，通过直接或间接损害胰岛素信号通路诱发IR。本文对脂质代谢中间产物调控骨骼肌胰岛素敏感性的研究进展进行综述，以期加深对糖尿病发病机制的理解与认识。

关键词： 骨骼肌; 脂质代谢中间产物; 胰岛素抵抗

Lipid metabolic intermediates regulate skeletal muscle insulin sensitivity

BAI Dan-Dan, XIAO Wei-Hua^*

Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China

Abstract

Skeletal muscle is the largest organ of human body, which completes 80%–90% of glucose intake stimulated by insulin, and is closely related to the occurrence and development of insulin resistance (IR). Skeletal muscle is one of the main places of lipid metabolism, and lipid metabolites participate in skeletal muscle metabolism as signal molecules. Fatty acids regulate skeletal muscle insulin sensitivity through insulin signaling pathway, inflammatory response and mitochondrial function. Saturated fatty acids (SFAs) induce insulin resistance by impairing insulin signal transduction, inducing mitochondrial dysfunction and inflammatory response, while unsaturated fatty acids reverse the adverse effects of SFAs and ameliorate IR by enhancing insulin signal transduction and anti-inflammatory effect. In addition, disorders of lipid metabolism in skeletal muscle cause accumulation of harmful metabolic intermediates, such as diacylglycerol, ceramide and long-chain acyl-coenzyme A, and induce IR by directly or indirectly damaging insulin signaling pathway. This article reviews the research progress of lipid metabolic intermediates regulating insulin sensitivity in skeletal muscle, which will help to better understand the pathogenesis of diabetes.

Key words: Skeletal muscle; lipid metabolic intermediates; insulin resistance

收稿日期：　　录用日期：

通讯作者：肖卫华　　E-mail: xiaoweihua@sus.edu.cn

DOI: 10.13294/j.aps.2022.0078

引用本文：

白丹丹, 肖卫华. 脂质代谢中间产物调节骨骼肌胰岛素敏感性[J]. 生理学报 2022; 74 (5): 805-815.

BAI Dan-Dan, XIAO Wei-Hua. Lipid metabolic intermediates regulate skeletal muscle insulin sensitivity. Acta Physiol Sin 2022; 74 (5): 805-815 (in Chinese with English abstract).