Cong Tao
Jianfei Pan
Lilan Zhang
Lulu Liu
Ying Zhao
Yiping Fan
Chunwei Cao
Jiali Liu
Jin Zhang
Sin Man Lam
Guanghou Shui
Wanzhu Jin
Wei Li
Jianguo Zhao
Kui Li
Yanfang Wang
1 State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
2 Department of Animal Science, China Agricultural University, Beijing 100193, China;
3 Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
4 College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, China;
5 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
6 Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China;
7 College of Life Sciences, Qingdao Agricultural University, Qingdao 266109, China
Funds: This research was funded by the National Natural Science Foundation of China (31672387), National Science Foundation for Distinguished Young Scholars (31925036), National Key Research and Development Program of China (2020YFC1316602), Sichuan Province & Chinese Academy of Science of Science & Technology Cooperation Project (2017JZ0025) and the Agricultural Science and Technology Innovation program (ASTIP-IAS05).
Received Date: 2020-02-15
Rev Recd Date:2020-07-05
Abstract
Abstract
RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat dietfed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.Keywords: RNF20,
fat loss,
adipose tissue development,
thermogenesis
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