Leucine metabolism is not altered with improved insulin sensitivity following a 6‐month exercise program in pre‐diabetics (LB447)

Abstract

Obesity is associated with decreased insulin sensitivity (IS), elevated plasma levels of branched‐chain amino acids (BCAAs), and accumulation of medium to long even‐chain acylcarnitines (AC; products of β‐oxidation). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight individuals. Whole‐body leucine turnover, IS and metabolic profiles were assessed from blood, muscle and breath samples at baseline in 10 healthy controls (CTRL: 5M, 5F; age 50 ± 3) and 9 overweight pre‐diabetic individuals (PD‐Pre: 5M, 4F; age 51 ± 2) using stable isotope tracers, hyperinsulinemic euglycemic clamp and metabolomics methods, respectively. PD then underwent a 6 month aerobic + resistance exercise program and repeated tests (PD‐Post). IS was higher in CTRL vs PD‐Pre, increased in PD‐Post, but remained lower than CTRL. Relative to lean mass, leucine breakdown, oxidation and synthesis were higher in PD‐Pre and PD‐Post vs CTRL, with no effect of exercise. Plasma leucine and valine were elevated in PD‐Pre vs CTRL and were not altered with exercise, while glycine was decreased in PD‐Pre vs CTRL, and increased in PD‐Post. Muscle AC were globally elevated in PD‐Pre vs CTRL and decreased in PD‐Post. We conclude exercise‐induced improvements in IS occur independent of changes in BCAA levels or metabolism, but are linked to decreased muscle AC levels, consistent with improved mitochondrial efficiency.Grant Funding Source: Supported by CV and Metabolic, a Pfizer research unit and NIH grant P01‐DK58398