Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice

Mol Endocrinol. 2016 Sep;30(9):988-95. doi: 10.1210/me.2015-1295. Epub 2016 Jul 18.


Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprandially, serving as regulators of the fed state in the liver. Here, we show that nuclear receptor Small Heterodimer Partner (SHP), a regulator of bile acid metabolism, impacts the endogenous peripheral clock by directly regulating Bmal1. Bmal1-dependent gene expression is altered in Shp knockout mice, and liver clock adaptation is delayed in Shp knockout mice upon restricted feeding. These results identify SHP as a potential mediator connecting nutrient signaling with the circadian clock.

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Animals
  • Cells, Cultured
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Immunoblotting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Nr5a2 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • nuclear receptor subfamily 0, group B, member 2