Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis

Cell Metab. 2019 Jul 2;30(1):92-110.e4. doi: 10.1016/j.cmet.2019.03.013. Epub 2019 Apr 18.


While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation is specific to exercise at the active phase. At the molecular level, HIF1α, a central regulator of glycolysis during hypoxia, is selectively activated in a time-dependent manner upon exercise, resulting in carbohydrate exhaustion, usage of alternative energy sources, and adaptation of systemic energy expenditure. Our findings demonstrate that the time of day is a critical factor to amplify the beneficial impact of exercise on both metabolic pathways within skeletal muscle and systemic energy homeostasis.

Keywords: HIF1α; circadian rhythms; energy homeostasis; exercise metabolism; glycolysis; lipid oxidation; metabolomics; skeletal muscle; transcriptomics.

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
  • Blotting, Western
  • Calorimetry, Indirect
  • Circadian Rhythm / physiology*
  • Energy Metabolism / physiology*
  • Glycolysis / genetics
  • Glycolysis / physiology
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lipid Peroxidation / genetics
  • Lipid Peroxidation / physiology
  • Male
  • Mass Spectrometry
  • Mice
  • Muscle, Skeletal / metabolism*
  • Physical Conditioning, Animal
  • Sequence Analysis, RNA
  • Software
  • Transcriptome / genetics


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit