Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity

	Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity
	Chu, YJ; Rosso, LG; Huang, P; Wang, ZC; Xu, YC; Yao, X; Bao, MH; Yan, J; Song, HY; Wang, G
刊名	CELL RESEARCH
	2014
卷号	24 期号:10 页码:1250-1265
关键词	FOXO1 liver Med23-knockout mice gluconeogenesis insulin resistance obesity diabetes
通讯作者	Wang, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,gwang@sibcb.ac.cn
英文摘要	Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	TRANSCRIPTION FACTOR FOXO1 ; PROTEIN-KINASE B ; MEDIATOR COMPLEX ; GENE-EXPRESSION ; HEPATIC GLUCONEOGENESIS ; INSULIN SENSITIVITY ; LEPTIN RECEPTOR ; RNA-SEQ ; SUBUNIT ; PHOSPHORYLATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000344993300012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/234]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chu, YJ,Rosso, LG,Huang, P,et al. Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity[J]. CELL RESEARCH,2014,24(10):1250-1265.
APA	Chu, YJ.,Rosso, LG.,Huang, P.,Wang, ZC.,Xu, YC.,...&Wang, G.(2014).Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity.CELL RESEARCH,24(10),1250-1265.
MLA	Chu, YJ,et al."Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity".CELL RESEARCH 24.10(2014):1250-1265.