Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression in...

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Published in:Scientific reports 2017-10, Vol.7 (1), p.14383-11, Article 14383
Main Authors: Mayeuf-Louchart, Alicia, Thorel, Quentin, Delhaye, Stéphane, Beauchamp, Justine, Duhem, Christian, Danckaert, Anne, Lancel, Steve, Pourcet, Benoit, Woldt, Estelle, Boulinguiez, Alexis, Ferri, Lise, Zecchin, Mathilde, Staels, Bart, Sebti, Yasmine, Duez, Hélène
Format: Article
Language:English
Subjects:
Adipogenesis
Animals
Atrophy
Autophagy
Cell Differentiation
Dexamethasone
Electron transport
Glucose metabolism
Lipid metabolism
Liver - metabolism
Mice
Mice, Knockout
Mitochondria
Muscle, Skeletal - metabolism
Muscular Atrophy - genetics
Muscular Atrophy - metabolism
Muscular Diseases - metabolism
Musculoskeletal system
Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics
Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism
Nuclear Receptor Subfamily 1, Group D, Member 1 - physiology
Overexpression
Phagocytosis
Repressor Proteins - genetics
Skeletal muscle
Thermogenesis
Transcriptional Activation
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Summary:The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression in skeletal muscle or its pharmacological activation improved mitochondrial respiration and enhanced exercise capacity. Here, in gain- and loss-of function studies, we show that Rev-erb-α also controls muscle mass. Rev-erb-α-deficiency in skeletal muscle leads to increased expression of the atrophy-related genes (atrogenes), associated with reduced muscle mass and decreased fiber size. By contrast, in vivo and in vitro Rev-erb-α over-expression results in reduced atrogenes expression and increased fiber size. Finally, Rev-erb-α pharmacological activation blocks dexamethasone-induced upregulation of atrogenes and muscle atrophy. This study identifies Rev-erb-α as a promising pharmacological target to preserve muscle mass.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-14596-2