Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle
Open accessAbstract
Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.
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The molecular clock is functional within human muscles.
“These results are consistent with the human data reported from two timepoints by Zambon et al. (2003) and demonstrate that the molecular clock is functional within human muscles (Perrin et al., 2018).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Perrin et al., 2018
Human vastus lateralis muscle biopsies over 24 h show clock gene expression with a pattern similar to the mouse model when considering active vs. inactive times of day.
“Similarly, in human studies, muscle biopsies over 24 h, find clock gene expression in the vastus lateralis muscle with a pattern similar to the mouse model when considering the active vs. inactive times of the day.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Perrin et al., 2018
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Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries
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Unacylated ghrelin, leptin, and appetite display diurnal rhythmicity in lean adults
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Circadian Rhythm Effects on the Molecular Regulation of Physiological Systems
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Genome-wide circadian regulation: A unique system for computational biology
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A Role for Exercise to Counter Skeletal Muscle Clock Disruption
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Resetting Time: The Role of Exercise Timing in Circadian Reprogramming for Metabolic Health
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Sex Inclusion in Transcriptome Studies of Daily Rhythms
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Running skeletal muscle clocks on time— the determining factors
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Physiological rhythms and metabolic regulation: Shining light on skeletal muscle
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Quantification of circadian rhythms in mammalian lung tissue snapshot data
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The Link Between Dietary Timing and Exercise Performance Through Adipocyte AMPKα2 Signaling
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Human genetic variation determines 24-hour rhythmic gene expression and disease risk
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- Authors
- Perrin, L., Loizides-Mangold, U., Chanon, S., Gobet, C., Hulo, N., Isenegger, L., Weger, B. D., Migliavacca, E., Charpagne, A., Betts, J. A., Walhin, J.-P., Templeman, I., Stokes, K., Thompson, D., Tsintzas, K., Robert, M., Howald, C., Riezman, H., Feige, J. N., Karagounis, L. G., Johnston, J. D., Dermitzakis, E. T., Gachon, F., Lefai, E., & Dibner, C.
- Affiliations
- University of Geneva (CH)
- Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland
- Inserm (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Nestlé Institute of Health Sciences, Lausanne, Switzerland
- University of Bath (GB)
- University of Nottingham (GB)
- Hôpital Edouard Herriot (FR)
- Institute of Genetics and Genomics of Geneva, Geneva, Switzerland
- Nestlé (Switzerland) (CH)
- University of Surrey (GB)
- CarMeN Laboratory, INSERM U1060, Oullins, France
- Corresponding author
- Dibner, Charna
- ORCID
- Loizides-Mangold, Ursula
- Chanon, Stéphanie
- Gobet, Cédric
- Hulo, Nicolas
- Weger, Benjamin D
- Migliavacca, Eugenia
- Charpagne, Aline
- Betts, James A
- Walhin, Jean-Philippe
- Templeman, Iain
- Stokes, Keith
- Thompson, Dylan
- Tsintzas, Kostas
- Robert, Maud
- Riezman, Howard
- Karagounis, Leonidas G
- Johnston, Jonathan D
- Dermitzakis, Emmanouil T
- Gachon, Frédéric
- Dibner, Charna
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-04-16
- Volume
- 7
- Pages
- 30
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5902165
- OpenAlex
- W2797820730
- Cited by
- 139
- References
- 108
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 24 · 2023: 15 · 2022: 17 · 2021: 16 · 2020: 24 · 2019: 12 · 2018: 5
- FWCI
- 8.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Sinergia Grant No. CRSII3-154405, 31003A-166700)
- Fondation Privée HUG
- Fondation Ernst et Lucie Schmidheiny
- Société Académique de Genève
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- circadian rhythm, circadian clock, skeletal muscle, rhythmic gene expression, myotubes, in vitro culture, GLUT4, glucose uptake, insulin signaling, lipid metabolism, glucose homeostasis
- MeSH terms
- Glucose, Humans, Muscle, Skeletal, Gene Expression Profiling, Lipid Metabolism, Metabolic Networks and Pathways, CLOCK Proteins, Circadian Clocks
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