eLife (Apr 2018)

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

  • Laurent Perrin,
  • Ursula Loizides-Mangold,
  • Stéphanie Chanon,
  • Cédric Gobet,
  • Nicolas Hulo,
  • Laura Isenegger,
  • Benjamin D Weger,
  • Eugenia Migliavacca,
  • Aline Charpagne,
  • James A Betts,
  • Jean-Philippe Walhin,
  • Iain Templeman,
  • Keith Stokes,
  • Dylan Thompson,
  • Kostas Tsintzas,
  • Maud Robert,
  • Cedric Howald,
  • Howard Riezman,
  • Jerome N Feige,
  • Leonidas G Karagounis,
  • Jonathan D Johnston,
  • Emmanouil T Dermitzakis,
  • Frédéric Gachon,
  • Etienne Lefai,
  • Charna Dibner

DOI
https://doi.org/10.7554/eLife.34114
Journal volume & issue
Vol. 7

Abstract

Read online

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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