Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists |
| |
Authors: | Solt Laura A Wang Yongjun Banerjee Subhashis Hughes Travis Kojetin Douglas J Lundasen Thomas Shin Youseung Liu Jin Cameron Michael D Noel Romain Yoo Seung-Hee Takahashi Joseph S Butler Andrew A Kamenecka Theodore M Burris Thomas P |
| |
Affiliation: | Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA. |
| |
Abstract: | Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-α and REV-ERB-β have an integral role in regulating the expression of core clock proteins driving rhythms in activity and metabolism. Here we describe the identification of potent synthetic REV-ERB agonists with in vivo activity. Administration of synthetic REV-ERB ligands alters circadian behaviour and the circadian pattern of core clock gene expression in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also altered, resulting in increased energy expenditure. Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|