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

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

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.

Citation

Perrin, L., Loizides-Mangold, U., Chanon, S., Gobet, C., Hulo, N., Isenegger, L., …Dibner, C. (2018). Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle. eLife, 7, Article e34114. https://doi.org/10.7554/elife.34114.001

• Journal Article Type: Article
• Acceptance Date: Apr 4, 2018
• Online Publication Date: Apr 16, 2018
• Publication Date: Apr 16, 2018
• Deposit Date: Nov 19, 2018
• Publicly Available Date: Nov 19, 2018
• Electronic ISSN: 2050-084X
• Publisher: eLife Sciences Publications
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Article Number: e34114
• DOI: https://doi.org/10.7554/elife.34114.001
• Public URL: https://nottingham-repository.worktribe.com/output/1284557
• Publisher URL: https://elifesciences.org/articles/34114#abstract
• Contract Date: Nov 19, 2018