CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice
2016-06
Source PublicationENDOCRINOLOGY
ISSN0013-7227
Volume157Issue:6Pages:2259-2269
Status已发表
DOI10.1210/en.2015-2027
AbstractCircadian 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.
Indexed BySCI
Language英语
Funding ProjectKnowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2014KIP106]
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000377214600008
PublisherENDOCRINE SOC
WOS KeywordHIGH-FAT DIET ; SKELETAL-MUSCLE ; MITOCHONDRIAL-FUNCTION ; GLUCOSE-METABOLISM ; ENERGY-METABOLISM ; CIRCADIAN CLOCK ; CALORIE RESTRICTION ; GENE-EXPRESSION ; RESISTANCE ; RESVERATROL
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1822
Collection生命科学与技术学院_特聘教授组_翟琦巍组
Corresponding AuthorZhai, Qiwei
Affiliation
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
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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.
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