Characterizing Human Oxidative, Anabolic and Glycolytic Metabolism in Athletes with Extreme Physiologies

Regular physical activity is known to benefit health but the long-term effects of specific exercise training on human metabolism remain incompletely described. In this study, we comprehensively characterized the blood metabolomes of male athletes with distinct exercise-adapted metabolic profiles, comparing endurance athletes (n = 11), sprinters (n = 8), and natural body builders (n = 9) as models for highly oxidative, glycolytic, and anabolic metabolism, respectively.

Serum samples of these athletes and a control group of male untrained individuals (n = 7) were collected both at rest and after maximum exercise. Using untargeted metabolomics profiling and weighted correlation network analysis, we examined associations of metabolites and metabolite modules with athlete groups and their characteristic traits (e.g., cardiovascular fitness or muscularity).

Our analyses revealed distinct metabolic signatures for the different groups: a highly anabolic metabolism was characterized by lower levels of sulfated steroids; a highly oxidative metabolism by higher levels of phospholipids; and a highly glycolytic metabolism by lower levels of sphingomyelins. In response to maximum exercise, 130 metabolites changed across all groups (e.g., N-lactoyl amino acids, acylcholines, energy metabolites), while 57 metabolites showed differences in magnitude or direction of change between groups (e.g., fatty acid oxidative products, cortisol).

Our findings demonstrate that exercise-induced adaptations in metabolism distinctly shape the human serum metabolome and influence the metabolic response to exercise. These insights are relevant for diseases driven by dysfunctional metabolism, such as impaired fat oxidation and dysregulated glycolysis (e.g., diabetes, dementia) and muscle wasting (e.g., sarcopenia), where our specialized populations may serve as useful models.