CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice

doi:10.1210/en.2015-2027

	CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice
	Liu, Jun 1; Zhou, Ben 1; Yan, Menghong 1; Huang, Rui 1; Wang, Yuangao 1; He, Zhishui 1; Yang, Yonggang 1; Dai, Changgui 1; Wang, Yiqian 1; Zhang, Fang 1; Zhai, Qiwei1,2
	2016-06
发表期刊	ENDOCRINOLOGY
ISSN	0013-7227
卷号	157 期号:6 页码:2259-2269
发表状态	已发表
DOI	10.1210/en.2015-2027
摘要	Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal muscle of Clock(Delta 19/Delta 19) mice, and knockdown of CLOCK or BMAL1 by small interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently, ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12 myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1), an important regulator of insulin sensitivity, in C2C12 myotubes and mouse skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its CLOCK-and BMAL1-dependent transcription in muscle cells. Further studies show that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice maintained in constant darkness, and resveratrol supplementation activates SIRT1 and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a potential valuable strategy to attenuate muscle insulin resistance related to circadian misalignment.
收录类别	SCI
语种	英语
资助项目	Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2014KIP106]
WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:000377214600008
出版者	ENDOCRINE SOC
WOS关键词	HIGH-FAT DIET ; SKELETAL-MUSCLE ; MITOCHONDRIAL-FUNCTION ; GLUCOSE-METABOLISM ; ENERGY-METABOLISM ; CIRCADIAN CLOCK ; CALORIE RESTRICTION ; GENE-EXPRESSION ; RESISTANCE ; RESVERATROL
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1822
专题	生命科学与技术学院_特聘教授组_翟琦巍组
通讯作者	Zhai, Qiwei
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Ctr Excellence Mol Cell Sci,Inst Nutr Sci, Shanghai 200031, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200093, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Liu, Jun,Zhou, Ben,Yan, Menghong,et al. CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice[J]. ENDOCRINOLOGY,2016,157(6):2259-2269.
APA	Liu, Jun.,Zhou, Ben.,Yan, Menghong.,Huang, Rui.,Wang, Yuangao.,...&Zhai, Qiwei.(2016).CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.ENDOCRINOLOGY,157(6),2259-2269.
MLA	Liu, Jun,et al."CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice".ENDOCRINOLOGY 157.6(2016):2259-2269.