Abstract 15168: Plasma Metabolomic Profiling Identifies Markers of Cardiorespiratory Fitness Responsive to Endurance Exercise Training

Background: High-throughput metabolite profiling allows for the assessment of thousands of metabolites that may participate in exercise-related pathways. Here, we characterize plasma metabolite changes in healthy individuals undergoing endurance exercise training (ET) to identify biochemical features of VO 2 max and/or those responsive to ET. Methods: We measured 444 known metabolites and 3221 non-targeted metabolite peaks using liquid chromatography tandem mass spectrometry and VO 2 max using CPET before and after 20 weeks of supervised, endurance ET in 654 sedentary participants (mean age=34y; 39% self-identified Black) from the HERITAGE Study. Multivariate linear regression assessed the relation between metabolites and baseline VO 2 max (ml·kg –1 ·min –1 ), adjusting for age, sex, and race. Changes after ET were determined using paired t tests. We used a false discovery rate (q) < 0.05 to determine statistical significance. Results: 494 metabolites were associated with VO 2 max, the majority (375/494) of which were non-targeted (unknown) metabolites with greater effect sizes than targeted peaks [β range: -29.66 - 17.80 and -22.76 - 12.87 for unknown and known metabolites]. We recapitulated known metabolite associations with VO 2 max including DMGV, branched chain amino acids, and uric acid ( Figure 1 ). 110 of 560 metabolites that changed after ET were associated with VO 2 max, including non-targeted peaks that concordantly changed after ET (e.g. metabolite peaks positively associated with VO 2 max that increased with ET; m/z 385.3056 and 695.5086; β for VO 2 max = 9.82 and -19.33, q= 5.56e-7 and 2.61e-17, and log fold-change = 0.03 and -0.01, q=9.58e-13 and 1.93e-4, respectively). Conclusions: We identified novel metabolite peaks associated with VO 2 max that concordantly changed after ET. Non-targeted metabolomic profiling reveals new markers related to VO 2 max and exercise response, motivating ongoing work to unambiguously identify these compounds.