ArticleSkeletal muscle2015
The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle.
Article in Skeletal muscle, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 167 citations in OpenAlex.
- Circadian phenotype is associated with diurnal variation in human exercise performance.European journal of applied physiology · 2026Trial
- Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans.Science advances · 2018Trial
- Stable clocks, rewired rhythms: circadian remodeling in skeletal muscle during aging, cachexia, and type 2 diabetes.Life metabolism · 2026Review
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Restoration of circadian rhythm as novel targets against sarcopenia.Chinese medical journal · 2026Review
- Timing the strain: skeletal muscle clock as regulator of physical activity.npj metabolic health and disease · 2026Review
- Housing Mice in Thermoneutrality Causes Tissue-specific Changes in Number, Identity, and Phase of Circadian-expressed mRNA Transcripts.bioRxiv : the preprint server for biology · 2026Article
- Chrono-Exercise Medicine: Why Biological Timing Matters for Human Health.Biomedicines · 2026Article
- β-Hydroxy-β-methylbutyrate (HMB) Counteracts Atrophy and Restores Circadian Rhythms in Myotubes.International journal of molecular sciences · 2026Article
- Circadian Regulation of Glucose Metabolism: Implications for Pathogenesis and Chronotherapy of Type 2 Diabetes.Diabetology · 2026Article
- Co-expression network analysis reveals repression ofbioRxiv : the preprint server for biology · 2026Article
- Chrono overexpression blunts exercise-induced improvement in muscular glucose metabolism by inhibiting the BMAL1 transcriptional activity in high-fat diet-fed mice.Journal of physiology and biochemistry · 2026Article
- Review
- Muscle-specific transcriptomic and metabolomic signatures reveal heterogeneous aging trajectories and altered intercellular communication in male murine skeletal muscle.Biogerontology · 2026Article
- Timing matters: circadian rhythm disruption in alcohol-associated peripheral organ pathophysiology.Function (Oxford, England) · 2026Review
- Physical exercise as a modulator of the sleep-obesity interaction: metabolic, neuroendocrine and circadian mechanisms.Frontiers in sleep · 2026Review
- Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health.Antioxidants (Basel, Switzerland) · 2025Review
- A Bayesian framework for genome-wide circadian rhythmicity biomarker detection.Briefings in bioinformatics · 2025Article
- HIF1α mediates circadian regulation of skeletal muscle metabolism and substrate preference in response to time-of-day exercise.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice.Nature communications · 2025Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSkeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. Within skeletal muscle exists an intrinsic molecular clock mechanism that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene expression in an inducible skeletal muscle-specific Bmal1 knockout mouse model (iMS-Bmal1 (-/-) ).
methodsWe used circadian statistics to analyze a publicly available, high-resolution time-course skeletal muscle expression dataset. Gene ontology analysis was utilized to identify enriched biological processes in the skeletal muscle circadian transcriptome. We generated a tamoxifen-inducible skeletal muscle-specific Bmal1 knockout mouse model and performed a time-course microarray experiment to identify gene expression changes downstream of the molecular clock. Wheel activity monitoring was used to assess circadian behavioral rhythms in iMS-Bmal1 (-/-) and control iMS-Bmal1 (+/+) mice.
resultsThe skeletal muscle circadian transcriptome was highly enriched for metabolic processes. Acrophase analysis of circadian metabolic genes revealed a temporal separation of genes involved in substrate utilization and storage over a 24-h period. A number of circadian metabolic genes were differentially expressed in the skeletal muscle of the iMS-Bmal1 (-/-) mice. The iMS-Bmal1 (-/-) mice displayed circadian behavioral rhythms indistinguishable from iMS-Bmal1 (+/+) mice. We also observed a gene signature indicative of a fast to slow fiber-type shift and a more oxidative skeletal muscle in the iMS-Bmal1 (-/-) model.
conclusionsThese data provide evidence that the intrinsic molecular clock in skeletal muscle temporally regulates genes involved in the utilization and storage of substrates independent of circadian activity. Disruption of this mechanism caused by phase shifts (that is, social jetlag) or night eating may ultimately diminish skeletal muscle's ability to efficiently maintain metabolic homeostasis over a 24-h period.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.