ShanghaiTech University Knowledge Management System
| CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice | |
| 2016-06 | |
| Source Publication | ENDOCRINOLOGY
 |
| ISSN | 0013-7227 |
| Volume | 157Issue:6Pages:2259-2269 |
| Status | 已发表 |
| DOI | 10.1210/en.2015-2027 |
| Abstract | 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. |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2014KIP106] |
| WOS Research Area | Endocrinology & Metabolism |
| WOS Subject | Endocrinology & Metabolism |
| WOS ID | WOS:000377214600008 |
| Publisher | ENDOCRINE SOC |
| WOS Keyword | HIGH-FAT DIET ; SKELETAL-MUSCLE ; MITOCHONDRIAL-FUNCTION ; GLUCOSE-METABOLISM ; ENERGY-METABOLISM ; CIRCADIAN CLOCK ; CALORIE RESTRICTION ; GENE-EXPRESSION ; RESISTANCE ; RESVERATROL |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://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 Author | Zhai, 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 Affilication | School 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. |
| Files in This Item: | Download All | |||||
| File Name/Size | DocType | Version | Access | License | ||
Edit Comment
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.