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

Article Article scientifique Article Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle eng 2018 author Perrin Laurent 671964 author Loizides-Mangold Ursula 668364 author Chanon Stéphanie author Gobet Cédric 645691 author Hulo Nicolas 29577 author Isenegger Laura 698793 author Weger Benjamin D author Migliavacca Voeffray Eugenia Linda 688727 author Charpagne Aline author Betts James A author Walhin Jean-Philippe author Templeman Iain author Stokes Keith author Thompson Dylan author Tsintzas Kostas author Robert Maude Ismay 60695 author Howald Cédric 510669 author Riezman Howard 134430 author Feige Jerome N author Karagounis Leonidas G author Johnston Jonathan D author Dermitzakis Emmanouil 542683 author Gachon Frédéric 543253 author Lefai Etienne author Dibner Charna 0000-0002-4188-803X 583541 e34114 10.7554/eLife.34114 29658882 2050-084X 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. RNA sequencing Circadian oscillators Human Human biology Human skeletal muscle Medicine Dewey 616 Dewey 540 Dewey 612 Dewey 590 Dewey 576.5 Swiss National Science Foundation Roles of the circadian oscillator in pancreatic islet function, failure and regeneration 166700 CH Project funding Swiss National Science Foundation Human muscle circadian rhythm and lipid homeostasis in physiology and insulin resistance 154405 CH Programmes 23 Institut de génétique et de génomique 0DH 39 Département de biochimie 144 134 Département de physiologie cellulaire et métabolisme 21C 135 Département de médecine génétique et développement 21D 56 Département de médecine 221 false 913 Endocrinologie et horloge circadienne 948 551 Population Genomics and Genetics of Complex Traits 892 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109825 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108539 eLife 7 9eb56714-9c5a-4975-8e6f-4970abbe15ad Article (Published version) Public elife-34114-v1.pdf 4268047 application/pdf CC BY openAccess Centres et instituts / Institut de génétique et de génomique Faculté des sciences / Section de chimie et biochimie / Département de biochimie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de médecine

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Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle	eLife			2018	543	200

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