title: PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.
abstract: Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) 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-1α 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-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-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-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Hatazawa
authors.affiliation: Department of Food Function and Labeling, National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tadaishi
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nagaike
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Morita
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Human Health and Design, Showa Women's University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ezaki
authors.affiliation: Department of Health Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Takai-Igarashi
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kitaura
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
authors.affiliation: Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D053858:Metabolic Networks and Pathways; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors