Leucine metabolism is not altered with improved insulin sensitivity following a 6-month exercise program in pre-diabetics

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 va...