Exploring the association of physical activity with the plasma and urine metabolome in adolescents and young adults

Abstract

Background: Regular physical activity elicits many health benefits. However, the underlying molecular mechanisms through which physical activity influences overall health are less understood. Untargeted metabolomics enables system-wide mapping of molecular perturbations which may lend insights into physiological responses to regular physical activity. In this study, we investigated the associations of habitual physical activity with plasma and urine metabolome in adolescents and young adults. Methods: This cross-sectional study included participants from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study with plasma samples n = 365 (median age: 18.4 (18.1, 25.0) years, 58% females) and 24 h urine samples n = 215 (median age: 18.1 (17.1, 18.2) years, 51% females). Habitual physical activity was assessed using a validated Adolescent Physical Activity Recall Questionnaire. Plasma and urine metabolite concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) methods. In a sex-stratified analysis, we conducted principal component analysis (PCA) to reduce the dimensionality of metabolite data and to create metabolite patterns. Multivariable linear regression models were then applied to assess the associations between self-reported physical activity (metabolic equivalent of task (MET)-hours per week) with single metabolites and metabolite patterns, adjusted for potential confounders and controlling the false discovery rate (FDR) at 5% for each set of regressions. Results: Habitual physical activity was positively associated with the “lipid, amino acids and xenometabolite” pattern in the plasma samples of male participants only (β = 1.02; 95% CI: 1.01, 1.04, p = 0.001, adjusted p = 0.042). In both sexes, no association of physical activity with single metabolites in plasma and urine and metabolite patterns in urine was found (all adjusted p > 0.05). Conclusions: Our explorative study suggests that habitual physical activity is associated with alterations of a group of metabolites reflected in the plasma metabolite pattern in males. These perturbations may lend insights into some of underlying mechanisms that modulate effects of physical activity.