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Publication : Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression.

First Author  Amador A Year  2016
Journal  PLoS One Volume  11
Issue  3 Pages  e0151014
PubMed ID  26963516 Mgi Jnum  J:249068
Mgi Id  MGI:6094149 Doi  10.1371/journal.pone.0151014
Citation  Amador A, et al. (2016) Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression. PLoS One 11(3):e0151014
abstractText  The nuclear receptors REV-ERBalpha and REV-ERBbeta are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes. The circadian rhythm is an endogenous mechanism, which generates entrainable biological changes that follow a 24-hour period. It regulates a number of physiological processes, including sleep/wakeful cycles and feeding behaviors. We recently demonstrated that REV-ERB-specific small molecules affect sleep and anxiety. The orexinergic system also plays a significant role in mammalian physiology and behavior, including the regulation of sleep and food intake. Importantly, orexin genes are expressed in a circadian manner. Given these overlaps in function and circadian expression, we wanted to determine whether the REV-ERBs might regulate orexin. We found that acute in vivo modulation of REV-ERB activity, with the REV-ERB-specific synthetic ligand SR9009, affects the circadian expression of orexinergic genes in mice. Long term dosing with SR9009 also suppresses orexinergic gene expression in mice. Finally, REV-ERBbeta-deficient mice present with increased orexinergic transcripts. These data suggest that the REV-ERBs may be involved in the repression of orexinergic gene expression.
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