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Publication
Mss51 deletion enhances muscle metabolism and glucose homeostasis in mice.
Authors Rovira Gonzalez YI, Moyer AL, LeTexier NJ, Bratti AD, Feng S, Sun C, Liu T, Mula
J, Jha P, Iyer SR, Lovering RM, O'Rourke B, Noh HL, Suk S, Kim JK, Essien Umanah
GK, Wagner KR
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal JCI insight
Year 2019
Date Published 10/1/2019
Volume : Pages 4 : Not Specified
PubMed Reference 31527314
Abstract Myostatin is a negative regulator of muscle growth and metabolism and its
inhibition in mice improves insulin sensitivity, increases glucose uptake into
skeletal muscle, and decreases total body fat. A recently described mammalian
protein called MSS51 is significantly downregulated with myostatin inhibition.
In vitro disruption of Mss51 results in increased levels of ATP, ß-oxidation,
glycolysis, and oxidative phosphorylation. To determine the in vivo biological
function of Mss51 in mice, we disrupted the Mss51 gene by CRISPR/Cas9 and found
that Mss51-KO mice have normal muscle weights and fiber-type distribution but
reduced fat pads. Myofibers isolated from Mss51-KO mice showed an increased
oxygen consumption rate compared with WT controls, indicating an accelerated
rate of skeletal muscle metabolism. The expression of genes related to oxidative
phosphorylation and fatty acid ß-oxidation were enhanced in skeletal muscle of
Mss51-KO mice compared with that of WT mice. We found that mice lacking Mss51
and challenged with a high-fat diet were resistant to diet-induced weight gain,
had increased whole-body glucose turnover and glycolysis rate, and increased
systemic insulin sensitivity and fatty acid ß-oxidation. These findings
demonstrate that MSS51 modulates skeletal muscle mitochondrial respiration and
regulates whole-body glucose and fatty acid metabolism, making it a potential
target for obesity and diabetes.




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