Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals.
ARNTL Transcription Factors
/ genetics
Adult
Aged
CLOCK Proteins
/ genetics
Circadian Clocks
/ genetics
Circadian Rhythm
/ physiology
Gene Expression
Humans
Insulin Resistance
/ physiology
Male
Middle Aged
Mitochondria
/ metabolism
Muscle Fibers, Skeletal
/ metabolism
Muscle, Skeletal
/ metabolism
Nuclear Receptor Subfamily 1, Group D, Member 1
/ genetics
Overweight
/ metabolism
Period Circadian Proteins
/ genetics
Day-night rhythm
Insulin resistance
Mitochondria
Skeletal muscle
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
16
04
2020
revised:
21
06
2020
accepted:
06
07
2020
pubmed:
14
7
2020
medline:
17
8
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Skeletal muscle mitochondrial function and energy metabolism displays day-night rhythmicity in healthy, young individuals. Twenty-four-hour 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 remains 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 5 time points (8 AM, 1 PM, 6 PM, 11 PM, 4 AM), 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-ERBα 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 during 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. NCT03733743.
Identifiants
pubmed: 32659272
pii: S2212-8778(20)30124-1
doi: 10.1016/j.molmet.2020.101050
pmc: PMC7415921
pii:
doi:
Substances chimiques
ARNTL Transcription Factors
0
BMAL1 protein, human
0
NR1D1 protein, human
0
Nuclear Receptor Subfamily 1, Group D, Member 1
0
Period Circadian Proteins
0
CLOCK Proteins
EC 2.3.1.48
Banques de données
ClinicalTrials.gov
['NCT03733743']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101050Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.
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