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Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle activates mTORC2, enhances glucose metabolism and muscle performance

Ruiz, Alexis and Dror, Erez and Handschin, Christoph and Furrer, Regula and Perez-Schindler, Joaquin and Bachmann, Christoph and Treves, Susan and Zorzato, Francesco. (2018) Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle activates mTORC2, enhances glucose metabolism and muscle performance. Scientific Reports, 8 (1). p. 636.

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Abstract

SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C dehydrogenase/ reductase family 7. Here we show that its over-expression in mouse skeletal muscles induces enhanced muscle performance in vivo, which is not related to alterations in excitation-contraction coupling but rather linked to enhanced glucose metabolism. Over-expression of SRP-35 causes increased phosphorylation of AktS473, triggering plasmalemmal targeting of GLUT4 and higher glucose uptake into muscles. SRP-35 signaling involves RARα and RARγ (non-genomic effect), PI3K and mTORC2. We also demonstrate that all-trans retinoic acid, a downstream product of the enzymatic activity of SRP-35, mimics the effect of SRP-35 in skeletal muscle, inducing a synergistic effect with insulin on AKTS473 phosphorylation. These results indicate that SRP-35 affects skeletal muscle metabolism and may represent an important target for the treatment of metabolic diseases.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2045-2322
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:18 Jun 2018 12:28
Deposited On:24 Jan 2018 13:24

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