RRC ID 61000
Author Ishikawa T, Kitaura Y, Kadota Y, Morishita Y, Ota M, Yamanaka F, Xu M, Ikawa M, Inoue N, Kawano F, Nakai N, Murakami T, Miura S, Hatazawa Y, Kamei Y, Shimomura Y.
Title Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.
Journal Sci Rep
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.
Volume 7
Pages 39825
Published 2017-1-4
DOI 10.1038/srep39825
PII srep39825
PMID 28051178
PMC PMC5209746
MeSH Adaptor Proteins, Signal Transducing Amino Acids, Branched-Chain / metabolism* Animals Carrier Proteins / metabolism Cell Cycle Proteins Diet, Protein-Restricted* Dietary Supplements Eukaryotic Initiation Factors Kidney / metabolism Mechanistic Target of Rapamycin Complex 1 / metabolism Mice Mice, Knockout Muscle Proteins / metabolism* Muscle, Skeletal / metabolism* Myocardium / metabolism Phosphoproteins / metabolism Phosphorylation Protein Kinases / deficiency Protein Kinases / genetics* Ribosomal Protein S6 Kinases, 90-kDa / metabolism
IF 3.998
Mice RBRC01834