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SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue

文献类型：期刊论文

作者Shuai, Lin1; Zhang, Li-Na1; Li, Bo-Han1,2; Tang, Chun-Lan1; Wu, Ling-Yan1; Li, Jia1; Li, Jing-Ya1
刊名DIABETES
出版日期2019-07-01
卷号68期号:7页码:1449-1461
ISSN号0012-1797
DOI10.2337/db18-1103
通讯作者Li, Jia(jli@simm.ac.cn) ; Li, Jing-Ya(jyli@simm.ac.cn)
英文摘要The unique thermogenic capacity of brown adipocyte makes it an attractive target for antiobesity treatments. Several epigenetic regulators can control brown adipocyte development. In this study, we show that SIRT5, a member of the sirtuins, is required for brown adipocyte differentiation and essential for brown adipogenic gene activation in vitro. Furthermore, we find out that knockdown of SIRT5 reduces intracellular alpha-ketoglutarate concentration, which leads to elevated H3K9me2 and H3K9me3 levels at promoter regions of Ppar gamma and Prdm16 loci. Finally, we discover that SIRT5 knockout mice on the Sv129 background exhibit less browning capacity in subcutaneous white adipose tissue compared with controls and show apparent cold intolerance, suggesting that SIRT5 can modulate the browning process in vivo. Thus, our study uncovers a new biological function of SIRT5 in brown adipocyte differentiation and a mechanism by which SIRT5 regulates brown adipogenic gene activation at least partly through an indirect effect on histone modifications. Our study extends the linkage between epigenetics and cell differentiation.
WOS关键词PPAR-GAMMA ; TRANSCRIPTIONAL CONTROL ; HISTONE DEMETHYLATION ; EPIGENETIC REGULATION ; CELL FATE ; BEIGE ; MOUSE ; DESUCCINYLATION ; THERMOGENESIS ; ADIPOGENESIS
资助项目National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81470166] ; National Program on Key Research Project[2016YFC1305505] ; Shanghai Commission of Science and Technology[16JC1405000] ; K.C. Wong Education Foundation
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:000473801400009
出版者AMER DIABETES ASSOC
源URL[http://119.78.100.183/handle/2S10ELR8/289258]  
专题新药研究国家重点实验室
通讯作者Li, Jia; Li, Jing-Ya
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Shuai, Lin,Zhang, Li-Na,Li, Bo-Han,et al. SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue[J]. DIABETES,2019,68(7):1449-1461.
APA Shuai, Lin.,Zhang, Li-Na.,Li, Bo-Han.,Tang, Chun-Lan.,Wu, Ling-Yan.,...&Li, Jing-Ya.(2019).SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue.DIABETES,68(7),1449-1461.
MLA Shuai, Lin,et al."SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue".DIABETES 68.7(2019):1449-1461.

入库方式： OAI收割

来源：上海药物研究所

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