| First Author | Hatazawa Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 3 | Pages | e91006 |
| PubMed ID | 24638054 | Mgi Jnum | J:215082 |
| Mgi Id | MGI:5604612 | Doi | 10.1371/journal.pone.0091006 |
| Citation | Hatazawa Y, et al. (2014) PGC-1alpha-mediated branched-chain amino acid metabolism in the skeletal muscle. PLoS One 9(3):e91006 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1alpha in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1alpha and cultured cells, we investigated whether PGC-1alpha stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1alpha specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain alpha-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1alpha. In C2C12 cells, the overexpression of PGC-1alpha significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1alpha in the skeletal muscle is considered to significantly contribute to BCAA metabolism. |
