Reshaping circadian metabolism in the suprachiasmatic nucleus and prefrontal cortex by nutritional challenge

Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29904-29913. doi: 10.1073/pnas.2016589117. Epub 2020 Nov 10.

Abstract

Food is a powerful entrainment cue for circadian clocks in peripheral tissues, and changes in the composition of nutrients have been demonstrated to metabolically reprogram peripheral clocks. However, how food challenges may influence circadian metabolism of the master clock in the suprachiasmatic nucleus (SCN) or in other brain areas is poorly understood. Using high-throughput metabolomics, we studied the circadian metabolome profiles of the SCN and medial prefrontal cortex (mPFC) in lean mice compared with mice challenged with a high-fat diet (HFD). Both the mPFC and the SCN displayed a robust cyclic metabolism, with a strikingly high sensitivity to HFD perturbation in an area-specific manner. The phase and amplitude of oscillations were drastically different between the SCN and mPFC, and the metabolic pathways impacted by HFD were remarkably region-dependent. Furthermore, HFD induced a significant increase in the number of cycling metabolites exclusively in the SCN, revealing an unsuspected susceptibility of the master clock to food stress.

Keywords: circadian clock; high-fat diet; metabolome reorganization; prefrontal cortex; suprachiasmatic nucleus.

Publication types

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

MeSH terms

  • Animals
  • Circadian Clocks / physiology*
  • Diet, High-Fat / adverse effects*
  • Male
  • Metabolome / physiology*
  • Metabolomics
  • Mice
  • Models, Animal
  • Photoperiod
  • Prefrontal Cortex / metabolism*
  • Suprachiasmatic Nucleus / metabolism*