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

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Title: 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.
Source: Nature. 5/3/2012, Vol. 485 Issue 7396, p62-68. 7p.
Subjects: Circadian rhythms, Metabolic disorders, Cardiovascular system abnormality prevention, Skeletal muscle, Adipose tissues, Substance P, Laboratory mice, Chemical agonists
Abstract: Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-? and REV-ERB-? 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. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: <searchLink fieldCode="AR" term="%22Solt%2C+Laura+A%2E%22">Solt, Laura A.</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Yongjun%22">Wang, Yongjun</searchLink><br /><searchLink fieldCode="AR" term="%22Banerjee%2C+Subhashis%22">Banerjee, Subhashis</searchLink><br /><searchLink fieldCode="AR" term="%22Hughes%2C+Travis%22">Hughes, Travis</searchLink><br /><searchLink fieldCode="AR" term="%22Kojetin%2C+Douglas+J%2E%22">Kojetin, Douglas J.</searchLink><br /><searchLink fieldCode="AR" term="%22Lundasen%2C+Thomas%22">Lundasen, Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Shin%2C+Youseung%22">Shin, Youseung</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Jin%22">Liu, Jin</searchLink><br /><searchLink fieldCode="AR" term="%22Cameron%2C+Michael+D%2E%22">Cameron, Michael D.</searchLink><br /><searchLink fieldCode="AR" term="%22Noel%2C+Romain%22">Noel, Romain</searchLink><br /><searchLink fieldCode="AR" term="%22Yoo%2C+Seung-Hee%22">Yoo, Seung-Hee</searchLink><br /><searchLink fieldCode="AR" term="%22Takahashi%2C+Joseph+S%2E%22">Takahashi, Joseph S.</searchLink><br /><searchLink fieldCode="AR" term="%22Butler%2C+Andrew+A%2E%22">Butler, Andrew A.</searchLink><br /><searchLink fieldCode="AR" term="%22Kamenecka%2C+Theodore+M%2E%22">Kamenecka, Theodore M.</searchLink><br /><searchLink fieldCode="AR" term="%22Burris%2C+Thomas+P%2E%22">Burris, Thomas P.</searchLink>
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  Data: Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-? and REV-ERB-? 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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