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WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPARγ serine 112

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Abstract

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.

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Abbreviations

aP2:

Adipocyte protein 2

C/EBP:

CCAAT/enhancer-binding protein

MRI:

Magnetic resonance imaging

PPAR:

Peroxisome proliferator-activated receptor

WIP1:

Wildtpye p53-induced phosphatase 1

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Acknowledgements

We greatly appreciate Dr. Zhi-Cheng Xiao for providing WIP1 KO mice strain, Dr. Kai Gao (Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences) for providing technical assistance in MRI assay, and the couple of Dr. Ming Shi and Dr. Dan Liu for providing technical supports in molecular biology.

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Authors and Affiliations

  1. Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China

    Dahu Li, Lijun Zhang, Lun Xu, Lili Liu, Yunling He, Yiyao Zhang, Xin Huang, Tong Zhao, Liying Wu, Yongqi Zhao, Kuiwu Wu, Shenghui Gong, Ming Fan & Lingling Zhu

  2. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China

    Ming Fan & Lingling Zhu

  3. Beijing Institute for Brain Disorders, Beijing, 100069, China

    Ming Fan

  4. Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, China

    Hui Li & Xiao Yu

  5. Navy General Hospital of PLA, Beijing, 100048, China

    Lili Liu

  6. Air Force General Hospital of PLA, Beijing, 100142, China

    Yiyao Zhang

  7. Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China

    Taiyun Zhao

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  1. Dahu Li
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Correspondence to Ming Fan or Lingling Zhu.

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Funding

This work was supported by Chinese National Basic Research Development Program (No. 2011CB910802) and National Natural Science Foundation of China (Nos. 31401000 and 81430044).

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The authors declare no conflict of interest.

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Li, D., Zhang, L., Xu, L. et al. WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPARγ serine 112. Cell. Mol. Life Sci. 74, 2067–2079 (2017). https://doi.org/10.1007/s00018-016-2450-4

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