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

Perrin, L, Loizides-Mangold, U, Chanon, S, Gobet, C, Hulo, N, Isenegger, L, Weger, B, Migliavacca, E, Charpagne, A, Betts, J , Walhin, J-P, Templeman, I, Stokes, K, Thompson, D, Tsintzas, K, Robert, M, Howald, C, Riezman, H, Feige, J, Karagounis, L, Johnston, Jonathan, Dermitzakis, E, Gachon, F, Lefai, E and Dibner, C (2018) Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle eLife, 7, e34114.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Perrin, L
Loizides-Mangold, U
Chanon, S
Gobet, C
Hulo, N
Isenegger, L
Weger, B
Migliavacca, E
Charpagne, A
Betts, J
Walhin, J-P
Templeman, I
Stokes, K
Thompson, D
Tsintzas, K
Robert, M
Howald, C
Riezman, H
Feige, J
Karagounis, L
Dermitzakis, E
Gachon, F
Lefai, E
Dibner, C
Date : 16 April 2018
Funders : BBSRC
DOI : 10.7554/eLife.34114
Copyright Disclaimer : Copyright Perrin et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Depositing User : Melanie Hughes
Date Deposited : 10 Apr 2018 09:09
Last Modified : 11 Dec 2018 11:24

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