Mss51 deletion enhances muscle metabolism and glucose homeostasis in mice
Date
2019Journal
JCI InsightPublisher
American Society for Clinical InvestigationType
Article
Metadata
Show full item recordAbstract
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, ?-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 ?-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 ?-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.Sponsors
National Institutes of Health, NIH: 5U2C-DK093000Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077396751&doi=10.1172%2fjci.insight.122247&partnerID=40&md5=5b5f9d512fa0af7c4c1ea0e340785ea5; http://hdl.handle.net/10713/11633ae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.122247
Scopus Count
Collections
Related articles
- Lack of skeletal muscle liver kinase B1 alters gene expression, mitochondrial content, inflammation and oxidative stress without affecting high-fat diet-induced obesity or insulin resistance.
- Authors: Chen T, Hill JT, Moore TM, Cheung ECK, Olsen ZE, Piorczynski TB, Marriott TD, Tessem JS, Walton CM, Bikman BT, Hansen JM, Thomson DM
- Issue date: 2020 Aug 1
- ACC2 Deletion Enhances IMCL Reduction Along With Acetyl-CoA Metabolism and Improves Insulin Sensitivity in Male Mice.
- Authors: Takagi H, Ikehara T, Kashiwagi Y, Hashimoto K, Nanchi I, Shimazaki A, Nambu H, Yukioka H
- Issue date: 2018 Aug 1
- Local myostatin inhibition improves skeletal muscle glucose uptake in insulin-resistant high-fat diet-fed mice.
- Authors: Eilers W, Chambers D, Cleasby M, Foster K
- Issue date: 2020 Jul 1
- Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance.
- Authors: Henstridge DC, Bruce CR, Drew BG, Tory K, Kolonics A, Estevez E, Chung J, Watson N, Gardner T, Lee-Young RS, Connor T, Watt MJ, Carpenter K, Hargreaves M, McGee SL, Hevener AL, Febbraio MA
- Issue date: 2014 Jun
- Mammalian Mss51 is a skeletal muscle-specific gene modulating cellular metabolism.
- Authors: Moyer AL, Wagner KR
- Issue date: 2015