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.
Sheng Li Xue Bao. 2020 Dec 25;72(6):804-816.
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.
当能量摄入超过能量消耗时，能量平衡紊乱是代谢综合征（MS）发生的主要危险因素。过氧化物酶体增殖物激活受体γ（PPARγ）辅激活因子-1α（PGC-1α）作为能量代谢的关键调节因子，已成为当前研究的热点。PGC-1α对环境刺激和营养信号敏感响应，并进一步选择性地与不同转录因子结合，以调节包括葡萄糖代谢、脂质代谢和生物钟等各种生理过程。在本综述中，我们描述了PGC-1α的基因和蛋白质结构，并综述了其在包括肝脏、骨骼肌和心脏等各种哺乳动物代谢器官中调节能量稳态的组织特异性功能。同时，我们总结了靶向PGC-1α的潜在小分子化合物在代谢疾病治疗中的应用。本综述将为代谢疾病的治疗提供理论依据和潜在的药物靶点。
