Mss51 deletion enhances muscle metabolism and glucose homeostasis in mice
Program in Molecular Medicine; Division of Endocrinology, Metabolism and Diabetes, Department of Medicine
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Endocrinology | Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists
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, beta-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 beta-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 beta-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.
Diabetes, Fatty acid oxidation, Glucose metabolism, Metabolism, Muscle Biology
DOI of Published Version
JCI Insight. 2019 Oct 17;4(20). pii: 122247. doi: 10.1172/jci.insight.122247. Link to article on publisher's site
Rovira Gonzalez YI, Noh HL, Suk S, Kim JK, Wagner KR. (2019). Mss51 deletion enhances muscle metabolism and glucose homeostasis in mice. Open Access Articles. https://doi.org/10.1172/jci.insight.122247. Retrieved from https://escholarship.umassmed.edu/oapubs/4018