246-OR: Role of Skeletal Muscle Branched-Chain Amino Acid Metabolism in Exercise Training–Induced Insulin Sensitivity

Abstract

Insulin sensitivity is enhanced by 3 months of either aerobic (high-intensity interval training, HIIT) or resistance exercise (RET) , but mechanisms leading to improved insulin sensitivity are not identical between modes of exercise. We sought to identify common predictors of exercise training-induced insulin sensitivity. Using RNAseq we found that branched chain amino acid (BCAA) and general amino acid metabolism were the only common pathways associated with enhanced insulin sensitivity by HIIT and RET in skeletal muscle. We explored the BCAA metabolism pathway and other amino acid metabolites as related to insulin sensitivity in response to HIIT and RET. Skeletal muscle and plasma were obtained from our previously published study which showed significantly enhanced insulin sensitivity following 12-weeks of either HIIT (n=19) or RET (n=18) . Immunoblotting was used to measure the abundance and phosphorylation of the key rate limiting enzyme in BCAA metabolism, branched chain ketoacid dehydrogenase (BCKDH) , in skeletal muscle. Liquid chromatography-mass spectrometry was used to measure amino acids and their metabolites before and after exercise training. Skeletal muscle BCKDH abundance and activity (indicated by reduced phosho/total BCKDH) were significantly increased (P<0.05) by both HIIT and RET. HIIT significantly increased (P<0.05) all three BCAAs (Ile +7.7 ± 2.2, Leu +18.9 ± 5.6, Val +24.5 ± 7.3 pmol/mg muscle) , as well as multiple other amino acids and metabolites in skeletal muscle. Although we did not detect an increase in amino acids or metabolites following RET in skeletal muscle, in plasma there was a significant increase (P<0.05) in all three aromatic amino acids (Phe +5.1 ± 2.2, Trp +5.6 ± 2.5, Tyr +4.8 ± 1.7 µM) as well as Pro (13.0 ± 4.6 µM) , Ala (+29.3 ± 12.1 µM) , and Met (2.1 ± 0.5 µM) following RET. These results suggest activation of amino acid metabolism pathways, contributing to enhanced insulin sensitivity following different modes of exercise training. Disclosure M.W.Pataky: None. A.Prabha kumar: n/a. M.M.Robinson: Stock/Shareholder; GE Healthcare Systems. K.Klaus: None. S.Dasari: None. K.Nair: None. Funding National Institutes of Health (RAG09531) National Institutes of Health (T32 DK007352)