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

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

  • EMBO Rep. 2024 Jan 22. doi: 10.1038/s44319-023-00028-y.
Penglin Li 1,  Jinlong Feng 1,  Hongfeng Jiang 1,  Xiaohua Feng 1,  Jinping Yang 1,  Yexian Yuan 1,  Zewei Ma 1,  Guli Xu 1,  Chang Xu 1,  Canjun Zhu 1,  Songbo Wang 1,  Ping Gao 1,  Gang Shu 2 3 4,  Qingyan Jiang 5 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Swine and Poultry Breeding, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China.
  • 2 State Key Laboratory of Swine and Poultry Breeding, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. shugang@scau.edu.cn.
  • 3 Guangdong Laboratory for Lingnan Modern Agricultural and Guangdong Province, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. shugang@scau.edu.cn.
  • 4 Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. shugang@scau.edu.cn.
  • 5 State Key Laboratory of Swine and Poultry Breeding, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. qyjiang@scau.edu.cn.
  • 6 Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. qyjiang@scau.edu.cn.
  • 7 National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, 510642, Guangzhou, Guangdong, China. qyjiang@scau.edu.cn.
PMID: 38253688 DOI: 10.1038/s44319-023-00028-y
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 transcriptomics analysis, we identified that the mechanism underlying the effects of DMA depends on the elevated intracellular acetyl-CoA content and increased Cyclin A acetylation rather than redox balance. This study reveals a novel mechanism by which gut microbes impair muscle angiogenesis and may provide a therapeutic target for skeletal muscle dysfunction in Cancer or aging.

Keywords

Acetylation; Angiogenesis; D-Malate; Skeletal Muscle; Vascular Endothelial Cells.

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