Nuclear receptor expression links the circadian clock to metabolism

Cell. 2006 Aug 25;126(4):801-10. doi: 10.1016/j.cell.2006.06.050.


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 TRalpha and beta 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / physiology
  • Animals
  • Biological Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Liver / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / physiology
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*


  • Receptors, Cytoplasmic and Nuclear