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能量代谢关键调控因子PGC-1α的研究进展

王慧婷, 张岩晨, 徐梦怡, 张雯翔, 刘畅, 陈思禹^*

中国药科大学生命科学与技术学院，南京 211198

摘要

能量代谢平衡的紊乱，即能量摄入超过消耗，是代谢综合征(metabolic syndrome, MS)的主要致病因素。过氧化物酶体增殖物激活受体γ共激活因子-1α (peroxisome proliferator activated receptor γ coactivator-1α, PGC-1α)作为能量代谢的关键调控因子，已成为当前研究的热点。它能够灵敏应答于各种环境刺激和营养信号的改变，并通过选择性地结合不同转录因子，协同控制包括葡萄糖稳态、脂质代谢平衡和生物时钟稳态在内的多种生理进程。本文回顾了PGC-1α基因和蛋白的结构，深度阐明了PGC-1α在肝脏、骨骼肌以及心脏等哺乳动物重要能量代谢器官中的组织特异性代谢调节功能。同时，我们还总结了以PGC-1α为潜在靶点的小分子化合物在代谢性疾病中的应用情况。本综述将为代谢性疾病的治疗提供扎实的理论依据和潜在药物治疗靶点。

关键词： 过氧化物酶体增殖物激活受体γ共激活因子-1α; 能量代谢; 组织特异性; 分子靶点; 药物

分类号：R339.6

Research progresses on PGC-1α, a key energy metabolic regulator 

WANG Hui-Ting, ZHANG Yan-Chen, XU Meng-Yi, ZHANG Wen-Xiang, LIU Chang, CHEN Si-Yu^*

College of Life Sciences, China Pharmaceutical University, Nanjing 211198, China

Abstract

Disturbance of the energy balance, when the energy intake exceeds its expenditure, is a major risk factor for the development of metabolic syndrome (MS). The peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) functions as a key regulator of energy metabolism and has become a hotspot in current researches. PGC-1α sensitively responds to the environmental stimuli and nutrient signals, and further selectively binds to different transcription factors to regulate various physiological processes, including glucose metabolism, lipid metabolism, and circadian clock. In this review, we described the gene and protein structure of PGC-1α, and reviewed its tissue-specific function in the regulation of energy homeostasis in various mammalian metabolic organs, including liver, skeletal muscle and heart, etc. At the meanwhile, we summarized the application of potential small molecule compounds targeting PGC-1α in the treatment of metabolic diseases. This review will provide theoretical basis and potential drug targets for the treatment of metabolic diseases.

Key words: peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α); energy metabolism; tissue specificity; molecular targets; drugs

收稿日期：2020-01-11　　录用日期：2020-05-06

通讯作者：陈思禹　　E-mail: siyuchen@cpu.edu.cn

DOI: 10.13294/j.aps.2020.0046

引用本文：

王慧婷, 张岩晨, 徐梦怡, 张雯翔, 刘畅, 陈思禹. 能量代谢关键调控因子PGC-1α的研究进展[J]. 生理学报 2020; 72 (6): 804-816.

WANG Hui-Ting, ZHANG Yan-Chen, XU Meng-Yi, ZHANG Wen-Xiang, LIU Chang, CHEN Si-Yu. Research progresses on PGC-1α, a key energy metabolic regulator . Acta Physiol Sin 2020; 72 (6): 804-816 (in Chinese with English abstract).