Regulation of Circadian Behavior and Metabolism by Synthetic REV-ERB Agonists
By Laura A. Solt, Yongjun Wang, Subhashish Banerjee, T. Hughes, D. Kojetin, T. Lundåsen, Y. Shin, Jin Liu, Michael D. Cameron, Romain Noel and 5 more. Nature, 2012
771 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems, Social Psychology
View Paper: https://www.semanticscholar.org/paper/1647d897a22676ee681553e4189ff7a175fe8943
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Citations in the corpus
- Timing to perfection: the biology of central and peripheral circadian clocks. (2012, background): “For example GSK4112 (SR6452) competes with heme for the binding to proteins of the REV-ERB family tomodulate adipogenesis in mice (Kumar et al., 2010) and SR9011 as well as SR9009 regulate circadian behavior and metabolism (Solt et al., 2012).”
- Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures (2016, positive): “REV-ERB agonists, for example, diminish adiposity, hyperglycemia, and hyperlipidemia in diet-induced obese mice (281).”