Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis

doi:10.1093/jmcb/mjz050

	Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis
	Zhao, Mingxia 2; Shen, Lihong 2; Ouyang, Zijun 2; Li, Manru 2; Deng, Guoliang 2; Yang, Chenxi 2; Zheng, Wei 2; Kong, Lingdong 2; Wu, Xuefeng 2; Wu, Xudong 2
刊名	JOURNAL OF MOLECULAR CELL BIOLOGY
	2020-04-01
卷号	12 期号:4 页码:277-290
关键词	hnRNP A1 insulin resistance hepatic steatosis glycogen synthesis
ISSN号	1674-2788
DOI	10.1093/jmcb/mjz050
通讯作者	Yin, Ye(yin.ye@163.com) ; Xu, Qiang(molpharm@163.com) ; Sun, Yang(yangsun@nju.edu.cn)
英文摘要	Impairment of glucose (Glu) uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions. The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis. Our results showed that conditional deletion of hnRNP A1 in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet (HFD). Conditional knockout mice fed a HFD showed exacerbated obesity, insulin resistance, and hepatic steatosis. In vitro interference of hnRNP A1 in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake, whereas hnRNP A1 overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin. The expression and stability of glycogen synthase (gys1) mRNA were also decreased in the absence of hnRNP A1. Mechanistically, hnRNP A1 interacted with gys1 and stabilized its mRNA, thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue. Taken together, our findings are the first to show that reduced expression of hnRNP A1 in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.
资助项目	National Natural Science Foundation of China[81673436] ; National Natural Science Foundation of China[91853109] ; National Natural Science Foundation of China[81872877] ; National Natural Science Foundation of China[91229109] ; State Key Laboratory of Drug Research[SIMM1903KF-10] ; Mountain-Climbing Talents Project of Nanjing University
WOS关键词	NUCLEAR RIBONUCLEOPROTEIN A1 ; GLYCOGEN-SYNTHASE KINASE-3 ; GLUCOSE-OXIDATION ; ADIPOSE-TISSUE ; PHOSPHORYLATION ; SITES ; REDISTRIBUTION ; AUTOANTIBODIES ; TRANSLATION ; INHIBITION
WOS研究方向	Cell Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000547594100004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291872]
专题	中国科学院上海药物研究所
通讯作者	Yin, Ye; Xu, Qiang; Sun, Yang
作者单位	1.Nanjing Med Univ, Dept Biochem & Mol Biol, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 210029, Peoples R China 2.Nanjing Univ, Sch Life Sci, Dept Biotechnol & Pharmaceut Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Mingxia,Shen, Lihong,Ouyang, Zijun,et al. Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2020,12(4):277-290.
APA	Zhao, Mingxia.,Shen, Lihong.,Ouyang, Zijun.,Li, Manru.,Deng, Guoliang.,...&Sun, Yang.(2020).Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis.JOURNAL OF MOLECULAR CELL BIOLOGY,12(4),277-290.
MLA	Zhao, Mingxia,et al."Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis".JOURNAL OF MOLECULAR CELL BIOLOGY 12.4(2020):277-290.