Sex dimorphism in serum lipid dynamics after acute exhaustive exercise

This study aimed to characterize serum lipidomic sexual dimorphism following acute exhaustive exercise under stringently controlled conditions. Forty healthy adults (20 males, 20 females) performed a CPET to exhaustion, with objective termination criteria and females tested during their mid-luteal phase. Untargeted lipidomics was performed on serum at baseline and at multiple postexercise time points. Males presented a greater absolute $\dot{\text{V}}$ O_2peak (45.05 ± 4.14 vs 36.80 ± 3.69 ml/kg/min, P < 0.001) but a comparable $\dot{\text{V}}$ O_2peak when FFM was normalized (56.50 ± 5.65 vs 55.45 ± 5.82 ml/kgFFM^/min, P = 0.567). This standardized exhaustion was validated by both sexes achieving similar, high-intensity termination criteria (P_RERpeak = 0.607, P_RPE = 0.176, P_HRpeak = 0.164). A total of 620 lipid species were identified via untargeted lipidomics. Sex-stratified analysis identified more significantly different lipids compared to pooled-sex analysis (male:179, female:288). Key sex-discriminating lipids included PE 36:4, PC 32:1, SM d18:1/25:0, BMP 34:1, and PC 36:4. Cluster analysis revealed three recovery patterns, with lipid distribution differing significantly by sex. This study demonstrates that distinct metabolic response patterns exist between sexes when standardized exhaustion is achieved. Sex-stratified analysis identified more sex-specific lipids and pinpointed five sex-discriminating lipid molecular markers. The study revealed three different lipid recovery patterns, establishing that identical physiological endpoints arise from distinct metabolic mechanisms and underscoring the importance of sex-stratified analysis in exercise metabolism research.