Serum metabolomic profiling of exercise response and hyperuricemia status in athletes: a two-part exploratory study

Abstract Background While high-intensity training improves physiological functions, it also induces significant metabolic stress, leading to a higher incidence of hyperuricemia among athletes compared to the general population. However, existing metabolomic studies on the association between high-intensity exercise and hyperuricemia remain limited, lacking mechanistic exploration of the link between acute exercise stress and chronic disease risk. This study aimed to investigate the potential metabolic associations between acute exercise stress and chronic hyperuricemia through using untargeted metabolomics, while identifying disease-related biomarkers. Methods This study employed LC-MS-based untargeted metabolomics. First, a self-controlled intervention was conducted in 41 normouricemic judo athletes to analyze immediate changes in serum metabolites before and immediately after high-intensity resistance exercise. Subsequently, a validation study was performed in a specific cohort to compare the resting metabolomic profiles between athletes with hyperuricemia and normouricemic controls. Results High-intensity resistance exercise induced significant alterations primarily in glycerophospholipid metabolism. Specifically, lysophosphatidylcholines (LysoPC) were markedly upregulated, whereas phosphatidylcholines (PC) were significantly downregulated immediately after exercise. LysoPC levels showed significant correlations with multiple clinical indices, and a subsequent comparative analysis between hyperuricemic and normouricemic athletes further identified differential metabolites closely associated with hyperuricemia risk. Conclusions This study explored the potential metabolic associations between acute exercise stress and chronic hyperuricemia. Key lipid metabolites, represented by LysoPC, hold promise as potential biomarkers. However, owing to the absence of recovery-phase data, the long-term relationship between these transient post-exercise changes and chronic hyperuricemia requires further validation. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2600126268. Registered 5 June 2026 (retrospectively registered).