CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1

• DOI: 10.1002/hep.26992
• Publication Date: 2014-01-18T09:11:00Z
• Authors: Ben Zhou; Yi Zhang; Fang Zhang; Yulei Xia; Jun Liu; Rui Huang; Yuangao Wang; Yanan Hu; Jingxia Wu; Changgui Dai; Hui Wang; Yanyang Tu; Xiaozhong Peng; Yiqian Wang; Qiwei Zhai
• Keywords: Mice, Knockout; 0301 basic medicine; ARNTL Transcription Factors; CLOCK Proteins; Down-Regulation; Darkness; Antioxidants; Circadian Rhythm; Mice; 03 medical and health sciences; Liver; Sirtuin 1; Resveratrol; Stilbenes; Hepatocytes; Animals; Insulin Resistance; Promoter Regions, Genetic

The protein deacetylase, sirtuin 1 (SIRT1), involved in regulating hepatic insulin sensitivity, shows circadian oscillation and regulates the clock. Recent studies show that misalignment leads to resistance (IR); however, underlying mechanisms are largely unknown. Here, we CLOCK brain muscle ARNT-like (BMAL1), two core transcription factors, correlated with sensitivity. Knockdown of or BMAL1 induces IR, whereas their ectopic expression attenuates IR. Moreover, change sensitivity is impaired Clock mutant, liver-specific Bmal1 knockout (KO) Sirt1 KO mice, required for SIRT1. Further CLOCK/BMAL1 binds SIRT1 promoter enhance its by In addition, constant darkness-induced mice decreases levels which can be dramatically reversed resveratrol. These findings offer new insights coordination clock metabolism hepatocytes regulation via CLOCK/BMAL1-dependent provide a potential application resveratrol combating misalignment-induced metabolic disorders.