title: Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity.
abstract: 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.
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: van Moorsel
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
authors.affiliation: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Frank A J L
authors.initials: FAJL
authors.lastname: Scheer
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Jörgensen
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Radiology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Vera B
authors.initials: VB
authors.lastname: Schrauwen-Hinderling
authors.affiliation: Univ Lille, Inserm, Institut Pasteur de Lille, UMR1011-EGID, BP245, 59019 Lille, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Duez
authors.affiliation: Univ Lille, Inserm, Institut Pasteur de Lille, UMR1011-EGID, BP245, 59019 Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands; CAPHRI School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Matthijs K C
authors.initials: MKC
authors.lastname: Hesselink
authors.affiliation: Univ Lille, Inserm, Institut Pasteur de Lille, UMR1011-EGID, BP245, 59019 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: p.schrauwen@maastrichtuniversity.nl.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
keywords: BMAL1, brain and muscle ARNT-like 1; BMI, body mass index; Biological rhythm; CLOCK, circadian locomotor output cycles kaput; CRY, cryptochrome; Energy metabolism; FCCP, carbonyl cyanide-4-trifluoromethoxyphenylhydrazone; Mitochondria; Molecular clock; NADH, reduced nicotinamide adenine dinucleotide; Oxidative capacity; PER, period; RER, respiratory exchange ratio; RT-QPCR, Real-Time Quantitative Polymerase Chain Reaction; Skeletal muscle; T2DM, type 2 diabetes mellitus; TCA cycle, tricarboxylic acid cycle