Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists

Laura A. Solt, Yongjun Wang, Subhashis Banerjee, Travis Hughes, Douglas J. Kojetin, Thomas Lundasen, Youseung Shin, Jin Liu, Michael D. Cameron, Romain Noel, Seung Hee Yoo, Joseph S. Takahashi, Andrew A. Butler, Theodore M. Kamenecka, Thomas P. Burris

Research output: Contribution to journalArticle

308 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)62-68
Number of pages7
JournalNature
Volume485
Issue number7396
DOIs
StatePublished - May 3 2012

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Metabolic Diseases
Ligands
Obese Mice
Cytoplasmic and Nuclear Receptors
Dyslipidemias
Circadian Rhythm
Hyperglycemia
Energy Metabolism
Hypothalamus
Adipose Tissue
Skeletal Muscle
Obesity
Fats
Diet
Gene Expression
Muscles
Liver
Health
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Solt, L. A., Wang, Y., Banerjee, S., Hughes, T., Kojetin, D. J., Lundasen, T., ... Burris, T. P. (2012). Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature, 485(7396), 62-68. https://doi.org/10.1038/nature11030

Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. / 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.

In: Nature, Vol. 485, No. 7396, 03.05.2012, p. 62-68.

Research output: Contribution to journalArticle

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 2012, 'Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists', Nature, vol. 485, no. 7396, pp. 62-68. https://doi.org/10.1038/nature11030
Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 May 3;485(7396):62-68. https://doi.org/10.1038/nature11030
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. / Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. In: Nature. 2012 ; Vol. 485, No. 7396. pp. 62-68.
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