Wefers 2020 Mol Metab

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Wefers J, Connell NJ, Fealy CE, Andriessen C, de Wit V, van Moorsel D, Moonen-Kornips E, Jörgensen JA, Hesselink MKC, Havekes B, Hoeks J, Schrauwen P (2020) Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals. Mol Metab [Epub ahead of print].

» PMID: 32659272 Open Access

Wefers Jakob, Connell Niels J, Fealy Ciaran E, Andriessen Charlotte, de Wit Vera, van Moorsel Dirk, Moonen-Kornips Esther, Joergensen Johanna A, Hesselink Matthijs K C, Havekes Bas, Hoeks Joris, Schrauwen Patrick (2020) Mol Metab

Abstract: Skeletal muscle mitochondrial function and energy metabolism displays day-night rhythmicity in healthy, young individuals. 24-h rhythmicity of metabolism has been implicated in the etiology of age-related metabolic disorders. Whether day-night rhythmicity in skeletal muscle mitochondrial function and energy metabolism is altered in older, metabolically comprised humans is so far unknown.

Twelve male overweight volunteers with impaired glucose tolerance and insulin sensitivity stayed in a metabolic research unit for 2 days under free living conditions with regular meals. Indirect calorimetry was performed at five time points (8AM, 1PM, 6PM, 11PM, 4AM), followed by a muscle biopsy. Mitochondrial oxidative capacity was measured in permeabilized muscle fibers using high-resolution respirometry.

Mitochondrial oxidative capacity did not display rhythmicity. The expression of circadian core clock genes BMAL1 and REV-ERBA showed a clear day-night rhythm (p < 0.001), peaking at the end of the waking period. Remarkably, the repressor clock gene PER2 did not show rhythmicity, whereas PER1 and PER3 were strongly rhythmic (p < 0.001). On the whole-body level resting energy expenditure was highest in the late evening (p < 0.001). Respiratory exchange ratio did not decrease in the night, indicating metabolic inflexibility.

Mitochondrial oxidative capacity does not show a day-night rhythm in older, overweight participants with impaired glucose tolerance and insulin sensitivity. In addition, gene expression of PER2 in skeletal muscle indicates that rhythmicity of the negative feedback loop of the molecular clock is disturbed. ClinicalTrials.gov ID: NCT03733743.

Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.


Bioblast editor: Plangger M O2k-Network Lab: NL Maastricht Schrauwen P


Labels: MiParea: Respiration, Comparative MiP;environmental MiP  Pathology: Obesity 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, NS  HRR: Oxygraph-2k 

2020-07