WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPARγ serine 112.
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. PPARγ is a master gene of adipogenesis, and the phosphorylation of PPARγ 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 PPARγ and dephosphorylating p-PPARγ S112 in vitro and in vivo.
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Dahu
D
Li
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Lijun
L
Zhang
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Lun
L
Xu
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.|Navy General Hospital of PLA, Beijing, 100048, China.
Lili
L
Liu
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Yunling
Y
He
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.|Air Force General Hospital of PLA, Beijing, 100142, China.
Yiyao
Y
Zhang
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Xin
X
Huang
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Tong
T
Zhao
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Liying
L
Wu
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Yongqi
Y
Zhao
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Kuiwu
K
Wu
Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, China.
Hui
H
Li
Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, China.
Xiao
X
Yu
Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Taiyun
T
Zhao
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
Shenghui
S
Gong
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China. fanming@nic.bmi.ac.cn.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. fanming@nic.bmi.ac.cn.|Beijing Institute for Brain Disorders, Beijing, 100069, China. fanming@nic.bmi.ac.cn.
Ming
M
Fan
Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China. linglingzhu@hotmail.com.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. linglingzhu@hotmail.com.
Lingling
L
Zhu
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D050154:Adiposity; D000818:Animals; D001835:Body Weight; D002460:Cell Line; D048429:Cell Size; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D020738:Leptin / Q000097:blood; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding; D000071636:Protein Phosphatase 2C / Q000172:deficiency / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D020738:Leptin; D047495:PPAR gamma; D014280:Triglycerides; D010768:Phosphoserine; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C
Adipogenesis; Adiposity; Dephosphorylation; PPARγ; WIP1 phosphatase