The role of bioactive lipids and eicosanoid metabolites in acute exercise in adults: Insights into human cardiorespiratory fitness

The molecular mechanisms underlying the salutary effects of exercise remain incompletely understood. Exerkines are signaling molecules with autocrine, paracrine, or endocrine effects released in response to exercise. Specific eicosanoids, small bioactive lipids, act as exerkines. Using a mass spectrometry-based platform, we assayed eicosanoids and related metabolites at rest and peak exercise in individuals undergoing cardiopulmonary exercise testing (CPET). We examined changes in metabolites with exercise and associations with cardiorespiratory fitness measured by peak VO₂ using multivariable linear regression. We studied 491 individuals (61% women, mean age 57 ± 15). We found 523 (59%) metabolites that dynamically changed with acute exercise (FDR q < 0.05). Of these, 278 (53%) including linoleic acid and arachidonic acid derivatives increased, and 245 (47%) decreased, including trihydroxyoctadecenoic acids (triHOMEs) and omega-3 fatty acids. For 39 metabolites, the magnitude of exercise-induced change correlated with peak VO₂, including omega-3 and omega-6 fatty acids and linoleic, palmitic, stearic, and arachidonic acid derivatives. We identified lipid metabolites underlying metabolomic responses to acute exercise that relate directly to cardiorespiratory fitness. Anti-inflammatory linoleic and arachidonic acid derivatives increased with exercise, while pro-inflammatory and pro-atherogenic triHOMEs decreased. Future studies may fully delineate metabolomic contributions to the effects of exercise including chronic exercise training.