Sexual dimorphism in the serum metabolome following acute exhaustive exercise

1. Males and females exhibit distinct serum metabolomic profiles when they reach standardized physiological exhaustion endpoints, with similar numbers of altered metabolites but different molecular compositions. 2. Lipid species composed the largest fraction of sex-differential responses, including LPLs, bile acids, and fatty acids, showing female-dominant sustained downregulation and male-dominant recoverable downregulation patterns. 3. Targeted analysis revealed the sexually antagonistic regulation of 37 triacylglycerol species. These species are characterized primarily by C50‒C52 carbon chain lengths and enrichment with monounsaturated fatty acids, particularly those containing palmitoleic acid. 4. Key metabolites showing sex-related differential characteristics, including hypoxanthine, sarcosine, and LPLs, were identified, providing molecular markers for sex differences in exercise responses. 5. Among the 115 metabolites correlated with V̇O_2peak, 41.7% exhibited opposing correlations between sexes, with L-kynurenine and androsterone sulfate as key examples, highlighting the necessity of sex-stratified analysis and the limitations of pooled approaches.