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

ABSTRACT: The 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. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. 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. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108539 | GEO | 2018/04/16

REPOSITORIES: GEO

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Temporal RNA-seq analysis of human skeletal myotubes synchronized in vitro

Project description:The 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. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. 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. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans.

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