The Circadian Clock in the Ventromedial Hypothalamus Controls Cyclic Energy Expenditure

Cell Metab. 2016 Mar 8;23(3):467-78. doi: 10.1016/j.cmet.2016.02.003.

Abstract

Organismal homeostasis relies on coherent interactions among tissues, specifically between brain-driven functions and peripheral metabolic organs. Hypothalamic circuits compute metabolic information to optimize energetic resources, but the role of the circadian clock in these pathways remains unclear. We have generated mice with targeted ablation of the core-clock gene Bmal1 within Sf1-neurons of the ventromedial hypothalamus (VMH). While this mutation does not affect the central clock in the suprachiasmatic nucleus (SCN), the VMH clock controls cyclic thermogenesis in brown adipose tissue (BAT), a tissue that governs energy balance by dissipating chemical energy as heat. VMH-driven control is exerted through increased adrenergic signaling within the sympathetic nervous system, without affecting the BAT's endogenous clock. Moreover, we show that the VMH circadian clock computes light and feeding inputs to modulate basal energy expenditure. Thus, we reveal a previously unsuspected circuit where an SCN-independent, hypothalamic circadian clock controls BAT function, energy expenditure, and thermogenesis.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Adipose Tissue, Brown / physiology
  • Adipose Tissue, White / physiology
  • Animals
  • Circadian Clocks
  • Circadian Rhythm
  • Energy Metabolism*
  • Homeostasis
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / metabolism
  • Period Circadian Proteins / physiology
  • Suprachiasmatic Nucleus / physiology*
  • Sympathetic Nervous System / physiology
  • Thermogenesis

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Period Circadian Proteins