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Rev-erb-α modulates skeletal muscle capacity

Type: Literature (pdf)

Submitter: [anonymous]

Category: Guides / Tutorials - Health / Medical

exhibition Date: 2017-01-22 07:09:46 MST

Views: 453

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Submitter's Comment
Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy Estelle Woldt1–5,9, Yasmine Sebti1–5,9, Laura A Solt6, Christian Duhem1–5, Steve Lancel4,7, Jérôme Eeckhoute1–5, Matthijs K C Hesselink8, Charlotte Paquet1–5, Stéphane Delhaye1–5, Youseung Shin6, Theodore M Kamenecka6, Gert Schaart8, Philippe Lefebvre1–5, Rémi Nevière4,7, Thomas P Burris6, Patrick Schrauwen8, Bart Staels1–5 & Hélène Duez1–5
The nuclear receptor Rev-erb-a modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-a is highly expressed in oxidative skeletal muscle and that its deficiency in muscle leads to reduced mitochondrial content and oxidative function, as well as upregulation of autophagy. These cellular effects resulted in both impaired mitochondrial biogenesis and increased clearance of this organelle, leading to compromised exercise capacity. On a molecular level, Rev-erb-a deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1–Ppargc-1a signaling pathway. These effects were recapitulated in isolated fibers and in muscle cells after knockdown of the gene encoding Rev-erb-a, Nr1d1. In complementary experiments, Rev-erb-a overexpression in vitro increased the number of mitochondria and improved respiratory capacity, whereas muscle overexpression or pharmacological activation of Rev-erb-a in vivo increased exercise capacity. This study identifies Rev-erb-a as a pharmacological target that improves muscle oxidative function by modulating gene networks controlling mitochondrial number and function.

Keywords: SR9009

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