Hepatic miR-378 targets p110 alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling

	Hepatic miR-378 targets p110 alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling
	Liu, W; Cao, HC; Ye, C; Chang, CJ; Lu, MH; Jing, YY; Zhang, D; Yao, X; Duan, ZJ; Xia, HF
刊名	NATURE COMMUNICATIONS
	2014
卷号	5 期号:1 页码:5684-5684
通讯作者	Ying, H (reprint author), Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Food Safety Res, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,yinghao@sibs.ac.cn
英文摘要	Understanding the regulation of insulin signalling in tissues provides insights into carbohydrate and lipid metabolism in physiology and disease. Here we show that hepatic miR-378/378* expression changes in response to fasting and refeeding in mice. Mice overexpressing hepatic miR-378/378* exhibit pure hepatic insulin resistance. miR-378 inhibits hepatic insulin signalling through targeting p110 alpha, a subunit of PI3K and hence a critical component of insulin signalling. Knockdown of hepatic p110 alpha mimics the effect of miR-378, while restoration of p110 alpha expression abolishes the action of miR-378 on insulin signalling as well as its systemic effects on glucose and lipid homeostasis. miR-378/378* knockout mice display hypoglycemia and increased hepatic triglyceride level with enhanced insulin sensitivity. Inhibition of hepatic p110 alpha in miR-378/378* knockout mice corrects the abnormal glucose tolerance. Finally, we show that overexpression of hepatic miR-378/378* ameliorates hepatic steatosis in ob/ob mice without exacerbating hyperglycemia. Our findings establish fasting-responsive miR-378 as a critical regulator of hepatic insulin signalling.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	METABOLIC-REGULATION ; RESISTANCE ; MICRORNAS ; RECEPTOR ; MICE ; SENSITIVITY ; EXPRESSION ; LIVER ; ACCUMULATION ; LIPOGENESIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000347609900002
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/286]
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	Liu, W,Cao, HC,Ye, C,et al. Hepatic miR-378 targets p110 alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling[J]. NATURE COMMUNICATIONS,2014,5(1):5684-5684.
APA	Liu, W.,Cao, HC.,Ye, C.,Chang, CJ.,Lu, MH.,...&Ying, H.(2014).Hepatic miR-378 targets p110 alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling.NATURE COMMUNICATIONS,5(1),5684-5684.
MLA	Liu, W,et al."Hepatic miR-378 targets p110 alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling".NATURE COMMUNICATIONS 5.1(2014):5684-5684.