title: Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.
abstract: Branched-chain amino acids (BCAAs) are essential amino acids for mammals and play key roles in the regulation of protein metabolism. However, the effect of BCAA deficiency on protein metabolism in skeletal muscle in vivo remains unclear. Here we generated mice with lower BCAA concentrations by specifically accelerating BCAA catabolism in skeletal muscle and heart (BDK-mKO mice). The mice appeared to be healthy without any obvious defects when fed a protein-rich diet; however, bolus ingestion of BCAAs showed that mTORC1 sensitivity in skeletal muscle was enhanced in BDK-mKO mice compared to the corresponding control mice. When these mice were fed a low protein diet, the concentration of myofibrillar protein was significantly decreased (but not soluble protein) and mTORC1 activity was reduced without significant change in autophagy. BCAA supplementation in drinking water attenuated the decreases in myofibrillar protein levels and mTORC1 activity. These results suggest that BCAAs are essential for maintaining myofibrillar proteins during protein undernutrition by keeping mTORC1 activity rather than by inhibiting autophagy and translation. This is the first report to reveal the importance of BCAAs for protein metabolism of skeletal muscle in vivo.
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Laboratory of Nutritional Biochemistry, 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: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kadota
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ota
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Yamanaka
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Minjun
authors.initials: M
authors.lastname: Xu
authors.affiliation: Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Graduate School of Health Sciences, Matsumoto University, Matsumoto, Nagano, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kawano
authors.affiliation: School of Human Cultures, University of Shiga Prefecture, Hikone, Shiga, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakai
authors.affiliation: Department of Nutrition, Shigakkan University, Obu, Aichi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.affiliation: Graduate School of Environmental and Life Science, Kyoto Prefectural University, Kyoto, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Hatazawa
authors.affiliation: 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, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D018753:Diet, Protein-Restricted; D019587:Dietary Supplements; D039642:Eukaryotic Initiation Factors; D007668:Kidney / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000597:Amino Acids, Branched-Chain; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D009124:Muscle Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase