Ma Xinran, Wang Dongmei, Zhao Wenjun, Xu Lingyan
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Front Endocrinol (Lausanne). 2018 Aug 21;9:473. doi: 10.3389/fendo.2018.00473. eCollection 2018.
Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-dependent transcription factor highly expressed in adipocytes, is a master regulator of adipogenesis and lipid storage, a central player in thermogenesis and an active modulator of lipid metabolism and insulin sensitivity. As a nuclear receptor governing numerous target genes, its specific signaling transduction relies on elegant transcriptional and post-translational regulations. Notably, in response to different metabolic stimuli, PPARγ recruits various cofactors and forms distinct transcriptional complexes that change dynamically in components and epigenetic modification to ensure specific signal transduction. Clinically, PPARγ activation via its full agonists, thiazolidinediones, has been shown to improve insulin sensitivity and induce browning of white fat, while undesirably induce weight gain, visceral obesity and other adverse effects. Thus, deciphering the combinatorial interactions between PPARγ and its transcriptional partners and their preferential regulatory network in the processes of development, function and senescence of adipocytes would provide us the molecular basis for developing novel partial agonists that promote benefits of PPARγ signaling without detrimental side effects. In this review, we discuss the dynamic components and precise regulatory mechanisms of the PPARγ-cofactors complexes in adipocytes, as well as perspectives in treating metabolic diseases via specific PPARγ signaling.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种在脂肪细胞中高度表达的配体依赖性转录因子，是脂肪生成和脂质储存的主要调节因子，是产热的核心参与者，也是脂质代谢和胰岛素敏感性的活跃调节因子。作为一种调控众多靶基因的核受体，其特定的信号转导依赖于精细的转录和翻译后调控。值得注意的是，响应不同的代谢刺激，PPARγ招募各种辅因子并形成不同的转录复合物，这些复合物在组成和表观遗传修饰方面动态变化，以确保特定的信号转导。临床上，通过其完全激动剂噻唑烷二酮激活PPARγ已被证明可改善胰岛素敏感性并诱导白色脂肪褐变，但会导致体重增加、内脏肥胖和其他不良影响。因此，破译PPARγ与其转录伙伴之间的组合相互作用及其在脂肪细胞发育、功能和衰老过程中的优先调控网络，将为我们开发新型部分激动剂提供分子基础，这些激动剂可促进PPARγ信号传导的益处而无有害副作用。在本综述中，我们讨论了脂肪细胞中PPARγ-辅因子复合物的动态组成和精确调控机制，以及通过特定PPARγ信号治疗代谢疾病的前景。
