标题：WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPAR gamma serine 112
作者：Li, Dahu; Zhang, Lijun; Xu, Lun; Liu, Lili; He, Yunling; Zhang, Yiyao; Huang, Xin; Zhao, Tong; Wu, Liying; Zhao, Yongqi; Wu, Kuiwu 更多 作者机构：[Li, Dahu; Zhang, Lijun; Xu, Lun; Liu, Lili; He, Yunling; Zhang, Yiyao; Huang, Xin; Zhao, Tong; Wu, Liying; Zhao, Yongqi; Wu, Kuiwu; Gong, Shenghui; F 更多
通讯作者：Fan, M;Zhu, LL;Fan, M;Zhu, LL;Fan, M
通讯作者地址：[Fan, M; Zhu, LL]Inst Basic Med Sci, Dept Cognit Sci, Beijing 100850, Peoples R China;[Fan, M; Zhu, LL]Nantong Univ, Coinnovat Ctr Neuroregenerat, Nan 更多
来源：CELLULAR AND MOLECULAR LIFE SCIENCES
关键词：Adipogenesis; Adiposity; Dephosphorylation; PPAR gamma; WIP1 phosphatase
摘要：WIP1, as a critical phosphatase, plays many important roles in various physiological and pathological processes through dephosphorylating different substrate proteins. However, the functions of WIP1 in adipogenesis and fat accumulation are not clear. Here, we report that WIP1-deficient mice show impaired body weight growth, dramatically decreased fat mass, and significantly reduced triglyceride and leptin levels in circulation. This dysregulation of adipose development caused by the deletion of WIP1 occurs as early as adipogenesis. In contrast, lentivirus-mediated WIP1 phosphatase overexpression significantly increases the adipogenesis of pre-adipocytes via an enzymatic activity-dependent mechanism. PPAR gamma is a master gene of adipogenesis, and the phosphorylation of PPAR gamma at serine 112 strongly inhibits adipogenesis; however, very little is known about the negative regulation of this phosphorylation. Here, we show that WIP1 phosphatase plays a pro-adipogenic role by interacting directly with PPAR gamma and dephosphorylating p-PPAR gamma S112 in vitro and in vivo.