Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
Article Details
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Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP
Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
Nature. 2012 Mar 29;485(7396):62-8. doi: 10.1038/nature11030.
- PubMed ID
- 22460951 [ View in PubMed]
- Abstract
Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-alpha and REV-ERB-beta 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions SR-9009 Nuclear receptor subfamily 1 group D member 1 Protein Humans UnknownAgonistDetails SR-9009 Nuclear receptor subfamily 1 group D member 2 Protein Humans UnknownAgonistDetails SR-9011 Nuclear receptor subfamily 1 group D member 1 Protein Humans UnknownAgonistDetails SR-9011 Nuclear receptor subfamily 1 group D member 2 Protein Humans UnknownAgonistDetails