Branched-Chain Amino Acid (BCAA) Metabolism, Insulin Sensitivity (IS), and Liver Fat Response to Exercise Training in Sedentary Prediabetic and Normoglycemic Men

Abstract

Studies suggest a role for BCAA in decreased IS and type 2 diabetes. Exercise improves IS, but the relationship with BCAA metabolism is unclear. We studied the effects of a 12 w exercise intervention on IS, liver fat and BCAA metabolism in prediabetic (n=13) and normoglycemic men (n=13). We estimated IS by hyperinsulinemic-euglycemic clamp, transcriptomics by mRNA-seq of skeletal muscle and adipose tissue biopsies, liver fat by MRI/MRS, and plasma (p)BCAA by HPLC, before and after the intervention. At baseline, liver fat and p-BCAA were higher, whereas IS and BCAA skeletal muscle and adipose tissue catabolism were lower in prediabetic vs. control men. Sum of pBCAA were elevated by 14% in prediabetic men and correlated negatively with IS (Figure A, p<0.05). Liver fat and adipose tissue BCAA catabolism correlated significantly to pBCAA levels. The exercise intervention increased IS by 29%, lowered liver fat by 25% and increased BCAA catabolism, whereas no significant change were observed in mean p-BCAA levels and changes did not correlate to changes in IS (Figure B). In conclusion, exercise intervention did not alter the mean pBCAA, despite significantly improved IS. We suggest that elevated pBCAA levels may not play a direct role causing insulin resistance, but rather is a consequence of accompanying alterations in liver, skeletal muscle and adipose tissue. Disclosure S. Lee: None. H.L. Gulseth: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck & Co., Inc., AstraZeneca. H. Refsum: None. T.M. Langleite: None. T. Holen: None. J. Jensen: None. C.A. Drevon: None. K.I. Birkeland: Research Support; Self; AstraZeneca, Novo Nordisk A/S, Eli Lilly and Company, Sanofi, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp..