RESISTANCE TRAINING FREQUENCY AND METABOLIC HEALTH: PRELIMINARY INSIGHTS FROM GLOBAL UNTARGETED METABOLOMICS

Consistent resistance training (RT) is a potent stimulus for skeletal muscle remodeling, metabolic flexibility, and long-term health. Beyond improvements in strength and body composition, frequent RT may reshape metabolism by enhancing mitochondrial efficiency, redox balance, and substrate utilization. Limited evidence describes how habitual RT frequency influences metabolic health at the metabolomic level. PURPOSE: To examine the relationship between RT frequency, metabolic health, and exploratory metabolomic profiles in healthy adults. METHODS: A cross-sectional sample of healthy men and women (N = 34; age 19–69 y) were grouped by self-reported RT frequency from the Physical Activity Vital Sign into high (HRT; ≥ 4 d/week; n = 24) or low (LRT; 0-1 d/week; n = 10). During a single visit, fasting blood was drawn and body composition was assessed by DXA. Insulin resistance was estimated by HOMA-IR. Group differences are reported as mean ± standard deviation and were assessed by ANCOVA. Untargeted plasma metabolomics were performed using the Metabolon Global Discovery Panel and analyzed with the Integrated Bioinformatics Platform. RESULTS: HRT participants were younger (28.4 ± 10.1 y, p < 0.01) and had lower %body fat (25.3 ± 8.0 %, p = 0.03) than LRT (44.2 ± 15.4 y; 36.2 ± 8.1%). HOMA-IR was lower in HRT (1.07 ± 0.51) compared to LRT (1.71 ± 0.73; p < 0.01), while fasting glucose did not differ between groups. PLS-DA scores plot showed distinct separation between HRT and LRT groups. No metabolites remained significant after FDR correction (lowest Q = 0.18). However, exploratory metabolomic profiling identified 126 metabolites differing (p < 0.05) between HRT and LRT groups. The dominant metabolic signature involved lipid (n = 55) and amino acid (n = 32) pathways. CONCLUSION: Higher habitual RT frequency was associated with greater insulin sensitivity independent of age, sex, and adiposity. Differences in glycerophospholipid and plasmalogen species suggest adaptive remodeling of membrane composition and improved oxidative resilience, while alterations in amino acids, indicate enhanced substrate flexibility and protein turnover. Together, these findings provide novel insight into biochemical pathways through which resistance training frequency may support metabolic health.