RGD Reference Report - The nuclear receptor Rev-erba controls circadian thermogenic plasticity. - Rat Genome Database

RGD Reference Report - The nuclear receptor Rev-erba controls circadian thermogenic plasticity. - Rat Genome Database

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General

The nuclear receptor Rev-erba controls circadian thermogenic plasticity.
Authors:	Gerhart-Hines, Zachary Feng, Dan Emmett, Matthew J Everett, Logan J Loro, Emanuele Briggs, Erika R Bugge, Anne Hou, Catherine Ferrara, Christine Seale, Patrick Pryma, Daniel A Khurana, Tejvir S Lazar, Mitchell A
Citation:	Gerhart-Hines Z, etal., Nature. 2013 Nov 21;503(7476):410-413. doi: 10.1038/nature12642. Epub 2013 Oct 27.
RGD ID:	13673837
Pubmed:	PMID:24162845 (View Abstract at PubMed)
PMCID:	PMC3839416 (View Article at PubMed Central)
DOI:	DOI:10.1038/nature12642 (Journal Full-text)
Circadian oscillation of body temperature is a basic, evolutionarily conserved feature of mammalian biology. In addition, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure. However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Here we show that the nuclear receptor Rev-erbα (also known as Nr1d1), a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown adipose tissue (BAT) function. Mice exposed to cold fare considerably better at 05:00 (Zeitgeber time¿22) when Rev-erbα is barely expressed than at 17:00 (Zeitgeber time¿10) when Rev-erbα is abundant. Deletion of Rev-erbα markedly improves cold tolerance at 17:00, indicating that overcoming Rev-erbα-dependent repression is a fundamental feature of the thermogenic response to cold. Physiological induction of uncoupling protein 1 (Ucp1) by cold temperatures is preceded by rapid downregulation of Rev-erbα in BAT. Rev-erbα represses Ucp1 in a brown-adipose-cell-autonomous manner and BAT Ucp1 levels are high in Rev-erbα-null mice, even at thermoneutrality. Genetic loss of Rev-erbα also abolishes normal rhythms of body temperature and BAT activity. Thus, Rev-erbα acts as a thermogenic focal point required for establishing and maintaining body temperature rhythm in a manner that is adaptable to environmental demands.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
negative regulation of cold-induced thermogenesis	involved_in	ISS	UniProtKB:Q3UV55	13673837	PMID:24162845	YuBioLab

Objects Annotated

Genes (Rattus norvegicus)

Nr1d1 (nuclear receptor subfamily 1, group D, member 1)

Additional Information