Skeletal muscle is responsible for ~70% of glucose uptake resulting from ingested carbohydrates ( DeFronzo et al., 1981 Gachon et al., 2017), and perturbations in glucose sensing and metabolism in this organ are strongly associated with insulin resistance in type 2 diabetes (T2D) ( Muoio and Newgard, 2008). As a result, metabolic processes in the liver, skeletal muscle, and other organs are subject to daily oscillations ( Asher and Sassone-Corsi, 2015) with the SCN keeping these rhythms in appropriate synchrony with each other. In turn, the central pacemaker orchestrates peripheral clocks through a combination of neuronal, endocrine, and metabolic signaling pathways ( Saini et al., 2015). The SCN clock is readjusted on a daily basis, mainly by light inputs coming from the retina. In mammals, the circadian system is driven by a central pacemaker, situated in the paired suprachiasmatic nuclei (SCN) of the hypothalamus, and by secondary oscillators located in peripheral organs. This mechanism ensures a temporal coordination of physiology and behavior with a near 24 hr period of rest-activity and feeding-fasting cycles, thus providing the organism with an evolutionary conserved advantage ( Albrecht, 2012 Spoelstra et al., 2016). Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.Ĭircadian rhythms are daily cycles of most bodily processes driven by a system of intrinsic biological clocks organized in a complex hierarchical manner. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. 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. 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. University of St Mark and St John, United Kingdom Ĭircadian regulation of transcriptional processes has a broad impact on cell metabolism.NCCR Chemical Biology, University of Geneva, Switzerland.Edouard Herriot University Hospital, France.University of Nottingham, United Kingdom.Ecole Polytechnique Fédérale de Lausanne, Switzerland.Nestlé Institute of Health Sciences, Switzerland.CarMeN Laboratory, INSERM U1060, France.Institute of Genetics and Genomics of Geneva, Switzerland.University Hospital of Geneva, Switzerland.
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