Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene

doi:10.1038/s41467-019-08585-4

	Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene
	Han, Yamei 1; Hu, Zhimin 1; Cui, Aoyuan 1; Liu, Zhengshuai 1; Ma, Fengguang 1; Xue, Yaqian 1; Liu, Yuxiao 1; Zhang, Feifei 1; Zhao, Zehua 2; Yu, Yanyan 3
刊名	NATURE COMMUNICATIONS
	2019-02-07
卷号	10 页码:13
ISSN号	2041-1723
DOI	10.1038/s41467-019-08585-4
通讯作者	Li, Yu(liyu@sibs.ac.cn)
英文摘要	Insulin-induced gene (Insig) negatively regulates SREBP-mediated de novo fatty acid synthesis in the liver. However, the upstream regulation of Insig is incompletely understood. Here we report that AMPK interacts with and mediates phosphorylation of Insig. Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662. AMPK-dependent phosphorylation ablates Insig's interaction with E3 ubiquitin ligase gp78 and represses its ubiquitination and degradation, whereas AMPK deficiency shows opposite effects. Interestingly, activation of AMPK by metformin causes an augmentation of Insig stability and reduction of lipogenic gene expression, and leads to the attenuation of hepatic steatosis in HFHS diet-fed mice. Moreover, hepatic overexpression of Insig-1 rescues hepatic steatosis in liver-specific AMPK alpha 2 knockout mice fed with HFHS diet. These findings uncover a novel effector of AMPK. Targeting Insig may have the therapeutic potential for treating fatty liver disease and related disorders.
资助项目	National Key R&D Program of China[2017YFC0909601] ; National Natural Science Foundation of China[31471129] ; National Natural Science Foundation of China[31671224] ; National Natural Science Foundation of China[81125023] ; Chinese Academy of Sciences[ZDBS-SSW-DQC-02] ; K.C. Wong Education Foundation
WOS关键词	ATTENUATE HEPATIC STEATOSIS ; IMPROVES HYPERLIPIDEMIA ; PROTEASOMAL DEGRADATION ; CHOLESTEROL-SYNTHESIS ; SREBP ; INSIG-1 ; PROTEIN ; HOMEOSTASIS ; MICE ; RESISTANCE
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000458008700002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290558]
专题	中国科学院上海药物研究所
通讯作者	Li, Yu
作者单位	1.Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci,Univ Chinese Acad Sci, Shanghai 200031, Peoples R China 2.Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Gastroenterol, Sch Med, Shanghai 200092, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Univ Chinese Acad Sci, Shanghai 201203, Peoples R China 4.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310014, Zhejiang, Peoples R China 5.Wuhan Univ, Hubei Key Lab Cell Homeostasis, Coll Life Sci, Inst Adv Studies, Wuhan 430072, Peoples R China
推荐引用方式 GB/T 7714	Han, Yamei,Hu, Zhimin,Cui, Aoyuan,et al. Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene[J]. NATURE COMMUNICATIONS,2019,10:13.
APA	Han, Yamei.,Hu, Zhimin.,Cui, Aoyuan.,Liu, Zhengshuai.,Ma, Fengguang.,...&Li, Yu.(2019).Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene.NATURE COMMUNICATIONS,10,13.
MLA	Han, Yamei,et al."Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene".NATURE COMMUNICATIONS 10(2019):13.