Temporal Dynamics of the Proteome and Metabolome in Response to Acute Endurance versus Resistance Exercise in Healthy Young Men

The health benefits of regular exercise stem from cumulative adaptations to repeated acute stress. However, the temporal molecular dynamics induced by a single session of endurance exercise (EE) versus resistance exercise (RE) remain poorly characterized, particularly in non-Western populations. We performed a randomized crossover trial in 15 healthy, young, exercise-naïve Chinese men. Participants completed a single session of EE and RE separated by a 7-day washout. Blood was collected at five time points (pre-exercise and 2, 15, 30, and 60 minutes postexercise) and analyzed using untargeted proteomic (454 proteins) and metabolomic (829 metabolites) analyses. Both exercise modes triggered rapid, time-dependent molecular changes, which we categorized into six temporal clusters, including rapid-sustained activation, transient suppression, and reversible recovery patterns. EE and RE commonly activated glycolysis (e.g., glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase) and purine metabolism (e.g., uric acid, xanthine) immediately postexercise, with effects sustained for 60 min. Notably, we observed distinct mode-specific temporal patterns. EE uniquely promoted fatty acid oxidation and induced transient suppression of immune-related proteins. Conversely, RE elicited a persistent enhancement of immune and inflammatory responses throughout recovery. Furthermore, vascular remodeling proteins (e.g., ECM1, FN1) were specifically upregulated during RE and at 60 min postexercise in both modalities. Our findings reveal that a single bout of EE and RE activates core energy pathways but diverges in the temporal regulation of lipid metabolism and immune function. EE favors fat oxidation with transient immune suppression, while RE promotes sustained immune activation. This time-resolved molecular map of acute exercise in a Chinese cohort provides a mechanistic rationale for optimizing personalized exercise prescriptions for chronic disease prevention.