Cited by 145Circadian rhythm and melatoninMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle

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Perrin, Laurent, Loizides-Mangold, Ursula, Chanon, Stéphanie, Gobet, Cédric, Hulo, Nicolas, Isenegger, Laura, Weger, Benjamin D, Migliavacca, Eugenia +17 more·2018·eLife

Abstract

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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  1. Bergstrom J 1962 Muscle Electrolytes in Man - Determined by Neutron Activation Analysis on Needle Biopsy Specimens - Study on Normal Subjects, Kidney Patients, and Patients with Chronic Diarrhoea Scandinavian Journal of Clinical and Laboratory Investigation 14

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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
Venue
eLife
Published
2018-04-16
Volume
7
Pages
30
ISSN
2050-084X (ISSN-L)
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
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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