Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity

Dirk van Moorsel, Jan Hansen, Bastiaan Havekes, Frank A. J. L. Scheer, J.A. Jorgensen, Joris Hoeks, Vera B. Schrauwen-Hinderling, Helene Duez, Philippe Lefebvre, Nicolaas C. Schaper, Matthijs K. C. Hesselink, Bart Staels, Patrick Schrauwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Objective: A disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not been investigated. Methods: Lean, healthy subjects were enrolled in a standardized living protocol with regular meals, physical activity and sleep to reflect our everyday lifestyle. Mitochondrial oxidative capacity was examined in skeletal muscle biopsies taken at five time points within a 24-hour period. Results: Core-body temperature was lower during the early night, confirming a normal day-night rhythm. Skeletal muscle oxidative capacity demonstrated a robust day-night rhythm, with a significant time effect in ADP-stimulated respiration (state 3 MO, state 3 MOG and state 3 MOGS, p <0.05). Respiration was lowest at 1 PM and highest at 11 PM (state 3 MOGS: 80.6 +/- 4.0 vs. 95.8 +/- 4.7 pmol/mg/s). Interestingly, the fluctuation in mitochondrial function was also observed in whole-body energy expenditure, with peak energy expenditure at 11 PM and lowest energy expenditure at 4 AM (p <0.001). In addition, we demonstrate rhythmicity in mRNA expression of molecular clock genes in human skeletal muscle. Conclusions: Our results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment.
Original languageEnglish
Pages (from-to)635-645
JournalMolecular Metabolism
Issue number8
Publication statusPublished - Aug 2016


  • Biological rhythm
  • Mitochondria
  • Oxidative capacity
  • Skeletal muscle
  • Energy metabolism
  • Molecular clock


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