Physiological significance of a peripheral tissue circadian clock

Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15172-7. doi: 10.1073/pnas.0806717105. Epub 2008 Sep 8.

Abstract

Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest-activity and fasting-feeding cycles, peripheral clocks are set by daily feeding, suggesting that at least some contribute metabolic regulation. The liver plays a well known role in glucose homeostasis, and we report here that mice with a liver-specific deletion of Bmal1, an essential clock component, exhibited hypoglycemia restricted to the fasting phase of the daily feeding cycle, exaggerated glucose clearance, and loss of rhythmic expression of hepatic glucose regulatory genes. We conclude that the liver clock is important for buffering circulating glucose in a time-of-day-dependent manner. Our findings suggest that the liver clock contributes to homeostasis by driving a daily rhythm of hepatic glucose export that counterbalances the daily cycle of glucose ingestion resulting from the fasting-feeding cycle.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Homeostasis / genetics
  • Liver / metabolism
  • Liver / physiology*
  • Mice
  • Mice, Mutant Strains

Substances

  • ARNTL Transcription Factors
  • Bmal1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Glucose