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

doi:10.2337/db18-1103

	SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue
	Shuai, Lin 1; Zhang, Li-Na 1; Li, Bo-Han 1,2; Tang, Chun-Lan 1; Wu, Ling-Yan 1; Li, Jia 1; Li, Jing-Ya 1
刊名	DIABETES
	2019-07-01
卷号	68 期号:7 页码:1449-1461
ISSN号	0012-1797
DOI	10.2337/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.
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关键词	PPAR-GAMMA ; TRANSCRIPTIONAL CONTROL ; HISTONE DEMETHYLATION ; EPIGENETIC REGULATION ; CELL FATE ; BEIGE ; MOUSE ; DESUCCINYLATION ; THERMOGENESIS ; ADIPOGENESIS
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	AMER DIABETES ASSOC
WOS记录号	WOS:000473801400009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289258]
专题	中国科学院上海药物研究所
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.