(P29-001-25) Metabolomic Responses Are More Pronounced in Muscle Than Serum After 28 Days of Arduous Exercise Plus Exogenous Erythropoietin

Objectives: Exogenous erythropoietin (EPO) administration combined with arduous exercise training increases hemoglobin mass (HM), V̇O₂peak, and 5-kilometer time trial performance (TT). The underlying metabolic adaptations contributing to these responses are unclear. This study assessed changes to serum and skeletal muscle metabolomes in response to 28 days of arduous exercise training with EPO.

Methods: Eight males (Age 20 ± 3 yrs, and BMI 25.17 ± 3.10kg/m²) completed this longitudinal study. Metabolomics analyses were conducted in serum and muscle samples collected before (PRE) and after (POST) 28 days of arduous exercise training (4x/week, exercise energy expenditures of 1334 ± 24 kcal/d) and EPO injections (50IU/kg, 3X/wk). Associations were assessed between significant metabolites and previously published outcomes: V̇O₂peak, TT, HM, and markers of whole body and skeletal muscle iron status using fold change (POST/PRE).

Results: Three serum metabolites (X-11849, cerotoylcarnitine (C26), and N-acetylputrescine) were significantly decreased (P < 0.05, FDR < 0.10) at POST compared to PRE. Eleven muscle metabolites decreased (P < 0.05, FDR < 0.10) and 24 increased (P < 0.05, FDR < 0.10) significantly at POST. Serum X-11849 was positively associated with V̇O₂peak (P < 0.05). Muscle myo-inositol was positively associated (P < 0.05) with HM, and TT. Methionine, n-acetlthreonine, and X-12015 were positively associated (P < 0.05) with muscle ferritin and stearoyl sphingomyelin was negatively associated (P < 0.05) with muscle transferrin receptor. Muscle 1-(1-enyl-stearoyl)-2-arachidonoyl-GPC (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-docosahexaenoyl-GPC (P-16:0/22:6), 1-(1-enyl-stearoyl)-2-docosahexaenoyl-GPC (P-18:0/22:6), and 1-(1-enyl-oleoyl)-2-docosahexaenoyl-GPC (P-18:1/22:6) were positively associated (P < 0.05) with V̇O₂peak.

Conclusions: Muscle metabolomic responses were more pronounced than serum, and associated with enhanced performance and oxygen carrying capacity. Mechanistically, many of the significantly different metabolites aid in energy production which may support the positive physiological adaptations to arduous exercise and EPO administration.

Funding Sources: DHP JPC-5/MOMRP; authors’ views not official US Army or DoD policy.