Abstract P2109: Sex Differences in the Plasma Metabolome Before and After Exercise Training

Background: Sex differences in metabolites, particularly their changes with exercise training, are largely unknown. We hypothesized that metabolites would not largely differ between males and females at baseline, but that most of the exercised-induced changes in metabolites would be sex-specific. Methods: Plasma metabolites were measured using untargeted LC-MS methods before and after a 20-week exercise intervention in participants from the HERITAGE Family Study (n=671, 56% Female, 35% Black, 17-65 yrs). A total of 810 metabolites were included. Sex differences at baseline were examined using Student t-tests. Paired t-tests were used to examine changes in metabolites with exercise training by sex. Significance was defined as FDR<0.05. Results: At baseline, the levels of 398 plasma metabolites were higher in males, while 155 were higher in females. The most significant sex differences were found for creatine, uric acid, and androsterone 3-glucuronide. Most exercise training changes in the plasma metabolome were sex-specific (74%, Fig 1A ). A majority of the female-specific metabolite changes were in carnitines and LPCs, with the highest individual changes in DG 30:1, CAR 10:2, and ectoine. Most of training changes observed only in males were in TGs, DGs, and PCs, with the greatest individual changes in PE 40:6, adenosine, and TG 54:9 ( Fig 1B ). Conclusions: Most of the plasma metabolites were different between sex groups at baseline, but importantly, a majority of the exercise-induced changes occurred in only males or females. The differential sex response of the plasma metabolome to exercise training observed in this study could represent important sex-specific metabolic pathway responses to an exercise intervention.