Effect of Obesity and Exercise on Amino Acid Metabolites in American-Indian Adolescents at Risk for Diabetes

Abstract

Circulating amino acids (AA) and their metabolites are biomarkers for insulin resistance and future diabetes in adults, but there are few, and conflicting findings in studies of adolescents. We performed amino acid metabolomic profiling in American Indian adolescents to determine whether specific analytes would vary with body composition and insulin sensitivity, and/or be altered in response to exercise training. Boys and girls, 11-18 years who were normal weight (NW, n=36) or obese (Ob, n=58) completed tests of fitness, body composition, and a fasting blood draw. Forty-two of the Ob group were retested after completing 16 weeks of aerobic exercise training. A panel of 42 plasma amino acids and metabolites were measured by UPLC/MS/MS. The Ob group had several risk factors for future diabetes, including higher body fat, lower aerobic fitness, and lower insulin sensitivity (iHOMA2). The Ob group had 16 analytes that were higher and 8 lower than the NW group. Among those that were higher in the Ob group were branched chain AAs (Val, Leu, Ile, +13-17%) and aromatic AAs (His, Phe, Tyr, +15-34%); those AAs were also correlated with body fat (r=0.32 to 0.53) and insulin sensitivity (r=-0.32 to -0.60). The Lys metabolite, α-aminoadipic acid, a predictor of diabetes in adults, was 46% higher in the Ob group and correlated with insulin sensitivity (r=-0.43). β-aminoisobutyric acid, a myokine related to insulin resistance in adults, was 29% lower in the Ob vs. the NW group and correlated with insulin sensitivity (r=0.32). Exercise training resulted in a 10% increase in aerobic fitness, but body composition and insulin sensitivity were unchanged. Only two AAs were changed (His, Cys) after training. These novel findings in adolescents demonstrate that several plasma AAs are altered by obesity and serve as biomarkers of insulin action, but are not altered with this exercise intervention. Disclosure K.R. Short: None. J. Chadwick: None. M.A. Tullier: None. L.D. Wolbert: None. C.L. Coleman: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc..