Nuclear Receptor Expression Links the Circadian Clock to Metabolism

Xiaoyong Yang, Michael Downes, Ruth T. Yu, Angie L. Bookout, Weimin He, Marty Straume, David J. Mangelsdorf, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

795 Scopus citations

Abstract

As sensors for fat-soluble hormones and dietary lipids, oscillations in nuclear receptor (NR) expression in key metabolic tissues may contribute to circadian entrainment of nutrient and energy metabolism. Surveying the diurnal expression profiles of all 49 mouse nuclear receptors in white and brown adipose tissue, liver, and skeletal muscle revealed that of the 45 NRs expressed, 25 are in a rhythmic cycle and 3 exhibit a single transient pulse of expression 4 hr into the light cycle. While thyroid hormones are generally constant, we find that TRα and β dramatically cycle, suggesting that fundamental concepts such as "basal metabolism" may require reexamination. The dynamic but coordinated changes in nuclear receptor expression, along with their key target genes, offers a logical explanation for known cyclic behavior of lipid and glucose metabolism and suggests novel roles for endocrine and orphan receptors in coupling the peripheral circadian clock to divergent metabolic outputs.

Original languageEnglish (US)
Pages (from-to)801-810
Number of pages10
JournalCell
Volume126
Issue number4
DOIs
StatePublished - Aug 25 2006

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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