mTORC1 is involved in the regulation of branched-chain amino acid catabolism in mouse heart

Abstract

The branched-chain α-ketoacid dehydrogenase (BCKDH) complex regulates branched-chain amino acid (BCAA) catabolism by controlling the second step of this catabolic pathway. In the present study, we examined the in vivo effects of treatment with an mTORC1 inhibitor, rapamycin, on cardiac BCKDH complex activity in mice. Oral administration of leucine in control mice significantly activated the cardiac BCKDH complex with an increase in cardiac concentrations of leucine and α-ketoisocaproate. However, rapamycin treatment significantly suppressed the leucine-induced activation of the complex despite similar increases in cardiac leucine and α-ketoisocaproate levels. Rapamycin treatment fully inhibited mTORC1 activity, measured by the phosphorylation state of ribosomal protein S6 kinase 1. These results suggest that mTORC1 is involved in the regulation of cardiac BCAA catabolism.