부산대학교 도서관

Introduction: The molecular pathways underlying the heterogeneous response to exercise in individuals at risk for cardiovascular disease remain unclear. Less is known about the molecular links to clinical outcomes including cardiorespiratory fitness and weight loss.Hypothesis: We hypothesized that dysregulated molecular pathways respond to exercise training and are associated with training-mediated outcomes.Methods: The study included 197 subjects with metabolic syndrome from the Studies of Targeted Risk Reduction Interventions through Defined Exercise (STRRIDE) clinical trials. Targeted quantitative metabolomic profiling of 15 amino acids and 45 acylcarnitines was performed in pre- and post-exercise plasma samples using a tandem MS/MS platform with addition of internal standards.Results: Principal-components analysis, used for multidimensional data reduction, identified 14 metabolite factors. Factor 1, composed of medium and long-chain acylcarnitines (MCAs and LCAs), and factor 3, composed of short-chain dicarboxylacylcarnitines (SCDAs), were increased after exercise training (p < .0001). Changes in factor 1 and 3 levels correlated with a change in RVO2peak (R = .15, p < .05 and R = .32, p < .01) and inversely correlated with changes in HOMA scores (R = -.27, p < .01 and R = -.22, p < .01). Factor 3 level changes also inversely correlated with other weight loss-related outcome changes including percent body fat (R = -0.21, p < .01), minimum waist circumference (R = -0.2, p < .01), body mass index (R = -.18, p < .05), and subcutaneous adipose tissue (R = -.16, p < .05). In multivariable models, factor 3 changes remained associated with an increase in RVO2peak(p = .0002), while changes in both factor 1 and 3 remained inversely associated with HOMA score changes (p = .0005 and p = .0004).Conclusions: Using metabolomic profiling in longitudinal samples from clinical trials of exercise in individuals with metabolic syndrome, we have identified known and novel molecular pathways that change with training-mediated clinical responses. Response associations with MCAs and LCAs link training-mediated changes to alterations in mitochondrial fatty acid oxidation, and associations with SCDAs suggest involvement of endoplasmic reticulum stress pathways.