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Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8565-E8574. doi: 10.1073/pnas.1705821114. Epub 2017 Sep 25.

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro.

Author information

1
Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, University of Geneva, CH-1211 Geneva, Switzerland.
2
Department of Cell Physiology and Metabolism, University of Geneva, CH-1211 Geneva, Switzerland.
3
Faculty Diabetes Centre, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
4
Section of Mathematics, University of Geneva, CH-1211 Geneva, Switzerland.
5
Department for Health, University of Bath, Bath BA2 7AY, United Kingdom.
6
CarMeN Laboratory, INSERM U1060, INRA 1397, University Lyon 1, 69600 Oullins, France.
7
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
8
Department of Digestive Surgery, Center of Bariatric Surgery, Edouard Herriot Hospital, 69003 Lyon, France.
9
Proteomics Core Facility, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
10
Experimental Myology and Integrative Biology Research Cluster, Faculty of Sport and Health Sciences, Plymouth Marjon University, Plymouth PL6 8BH, United Kingdom.
11
Institute of Nutritional Science, Nestlé Research Centre, CH-1015 Lausanne, Switzerland.
12
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
13
School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
14
Department of Biochemistry, University of Geneva, CH-1211 Geneva, Switzerland; Howard.Riezman@unige.ch charna.dibner@hcuge.ch.
15
National Centre of Competence in Research Chemical Biology, University of Geneva, CH-1211 Geneva, Switzerland.
16
Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, University of Geneva, CH-1211 Geneva, Switzerland; Howard.Riezman@unige.ch charna.dibner@hcuge.ch.

Abstract

Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.

KEYWORDS:

circadian clock; human primary myotubes; human skeletal muscle; lipid metabolism; lipidomics

PMID:
28973848
PMCID:
PMC5642690
DOI:
10.1073/pnas.1705821114
[Indexed for MEDLINE]
Free PMC Article

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