Microbiota derived D-malate inhibits skeletal muscle growth and angiogenesis during aging via acetylation of Cyclin A.

ABSTRACT: Metabolites derived from the intestinal microbiota play an important role in maintaining skeletal muscle growth, function, and metabolism. Here, we found that D-malate (DMA) is produced by mouse intestinal microorganisms and its levels increase during aging. Moreover, we observed that dietary supplementation of 2% DMA inhibits metabolism in mice, resulting in reduced muscle mass, strength, and the number of blood vessels, as well as the skeletal muscle fiber type I/IIb ratio. In vitro assays demonstrate that DMA decreases the proliferation of vascular endothelial cells and suppresses the formation of blood vessels. In vivo, we further demonstrated that boosting angiogenesis by muscular VEGFB injection rescues the inhibitory effects of D-malate on muscle mass and fiber area. By transcriptom

SUBMITTER: Li P 

PROVIDER: S-EPMC10897302 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature