Journal
ELIFE
Volume 12, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.81858
Keywords
MSTN; skeletal muscle; gut microbiota; short chain fatty acids; porcine; Mouse
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The host genome and intestinal microbiota have mutual influences on each other. Deletion of the myostatin (MSTN) gene in pigs positively regulates the expression of tight junction-related genes in the intestine, leading to changes in the structure of the intestinal microbiota. Transplantation of the intestinal microbiota from MSTN-deficient pigs into mice resulted in increased muscle growth and higher levels of short-chain fatty acids.
The host genome may influence the composition of the intestinal microbiota, and the intestinal microbiota has a significant effect on muscle growth and development. In this study, we found that the deletion of the myostatin (MSTN) gene positively regulates the expression of the intestinal tight junction-related genes TJP1 and OCLN through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of MSTN-/- pigs differed from wild-type, including by the presence of a thicker muscularis and longer plicae. Together, these changes affect the structure of intestinal microbiota. Mice transplanted with the intestinal microbiota of MSTN-/- pigs had myofibers with larger cross-sectional areas and higher fast-twitch glycolytic muscle mass. Microbes responsible for the production of short-chain fatty acids (SCFAs) were enriched in both the MSTN-/- pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We also demonstrated that valeric acid stimulates type IIb myofiber growth by activating the Akt/mTOR pathway via G protein-coupled receptor 43 and ameliorates dexamethasone-induced muscle atrophy. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.
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