Serum proteomics in elite athletes reveals divergent adaptations to endurance vs. strength training

Elite training induces profound physiological adaptations, yet whether these changes manifest as stable circulating proteomes remains unclear. This study characterized serum proteomic profiles in male and female Olympic-level athletes to identify biomarkers associated with long-term endurance and strength training. Cross-sectional study in Olympic-level athletes and sedentary controls. Resting serum samples were collected from male and female marathon runners and weightlifters (with 5–15 years of training), alongside age- and sex-matched sedentary individuals. Proteomic profiling was performed using tandem mass spectrometry. Data were processed with MaxQuant and analyzed using Perseus. Selected proteins were confirmed using antibody-based assays. Among 301 identified protein groups, 36 showed significant differences between groups. Apolipoprotein A-IV (APOA4) was elevated in athletes, particularly marathoners, suggesting cardiovascular adaptation to endurance training. Fibronectin 1 (FN1) was reduced in weightlifters, consistent with vascular remodeling associated with resistance training. Marathoners exhibited higher levels of von Willebrand factor (VWF) and glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), and lower levels of galectin-3-binding protein (LGALS3BP) and leucine-rich alpha-2-glycoprotein 1 (LRG1), indicating immunomodulatory effects of oxidative training. Weightlifters showed reduced levels of GPLD1 and extracellular matrix protein 1 (ECM1), reflecting distinct remodeling pathways. FN1, APOA4, VWF, LGALS3BP and ECM1 levels were further confirmed. Endurance and resistance training elicit modality-specific serum proteomic adaptations that reflect vascular, endothelial, and hemostatic remodeling. These molecular signatures, observed in both sexes, highlight stable changes induced by chronic training and may inform cardiovascular prevention strategies and evidence-based approaches in sports science to optimize training and performance.