Metabolic plasticity and obesity-associated changes in diurnal postexercise metabolism in mice

Metabolism. 2024 Jun:155:155834. doi: 10.1016/j.metabol.2024.155834. Epub 2024 Mar 11.

Abstract

Background: Circadian disruption is widespread and increases the risk of obesity. Timing of therapeutic interventions may promote coherent and efficient gating of metabolic processes and restore energy homeostasis.

Aim: To characterize the diurnal postexercise metabolic state in mice and to identify the influence of diet-induced obesity on identified outcomes.

Methods: C57BL6/NTac male mice (6 wks of age) were fed a standard chow or high-fat diet for 5 weeks. At week 5, mice were subjected to a 60-min (16 m/min, 5 % incline) running bout (or sham) during the early rest (day) or early active (night) phase. Tissue and serum samples were collected immediately post-exercise (n = 6/group). In vivo glucose oxidation was measured after oral administration of 13C-glucose via 13CO2 exhalation analysis in metabolic cages. Basal and isoproterenol-stimulated adipose tissue lipolysis was assessed ex vivo for 1 h following exercise.

Results: Lean mice displayed exercise-timing-specific plasticity in metabolic outcomes, including phase-specificity in systemic glucose metabolism and adipose-tissue-autonomous lipolytic activity depending on time of day. Conversely, obesity impaired temporal postexercise differences in whole-body glucose oxidation, as well as the phase- and exercise-mediated induction of lipolysis in isolated adipose tissue. This obesity-induced alteration in diurnal metabolism, as well as the indistinct response to exercise, was observed concomitant with disruption of core clock gene expression in peripheral tissues.

Conclusions: Overall, high-fat fed obese mice exhibit metabolic inflexibility, which is also evident in the diurnal exercise response. Our study provides physiological insight into exercise timing-dependent aspects in the dynamic regulation of metabolism and the influence of obesity on this biology.

Keywords: Adipose tissue; Circadian rhythm; Exercise; Lipolysis; Time of day.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Circadian Rhythm* / physiology
  • Diet, High-Fat* / adverse effects
  • Energy Metabolism / physiology
  • Glucose / metabolism
  • Lipolysis
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Obesity* / metabolism
  • Physical Conditioning, Animal* / physiology

Substances

  • Glucose