Metabolic flexibility and liver function following leucine supplementation during caloric restriction

Abstract Background. Metabolic flexibility (MF) is the capacity to switch from fat to carbohydrate utilization when required, and MF is constrained in the metabolic syndrome (MetS). We determined whether l-leucine (Leu) supplementation enhanced resting energy expenditure (REE), respiratory quotient (RQ), MF, insulin sensitivity and liver function during caloric restriction (CR). Methods. Thirty-seven participants at risk of MetS completed a parallel, double-blind RCT comparing Leu vs placebo during CR. REE and RQ were measured before and every 15 min for 2hr following an OGTT. Blood samples were assayed for clinical chemistry, liver function tests (LFT) and fibroblast growth factor 21 (FGF21). Stumvoll’s insulin sensitivity index (ISI), fatty liver index (FLI) and integrated area under response curves were calculated for REE (iREE) and RQ (iRQ). Metabolic flexibility was defined by iRQ following the OGTT. All measurements were made at the start and end of the trial. Results. Adjusted for pre-trial values and other covariates, fasting REE, RQ, ISI, LFTs, FLI or FGF21 were not different. There were no differences in postprandial iREE, 2hr_FGF21 or 2hr_ISI. However, Leu resulted in a significantly greater iRQ following CR. Partial correlations indicated that iRQ was significantly related to 2hr_ISI (r = 0.53;p = 0.002) and negatively to fasting alanine amino transferase (ALT) (r= -0.52;p = 0.001). iREE was significantly but negatively related to other liver function parameters. Conclusion. Leu supplementation improved MF over CR but did not impact REE, ISI and liver function. Overall, there were significant interrelationships between energy metabolism, ISI and liver function.