Combined Aerobic and Resistance Training Improves Metabolic Health and Is Associated with Arginine and Histidine Metabolic Changes During the Transition from Metabolically Unhealthy to Metabolically Healthy Obesity in Young Adults

Background: Exercise training is known to improve metabolic health in individuals with obesity; however, its role in facilitating transitions between metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO), as well as the associated metabolic adaptations, remains incompletely understood. Methods: A total of 84 young adults with obesity were enrolled and classified MUO (n = 55) or MHO (n = 29) based on baseline metabolic profiles. All participants completed an 8-week supervised exercise intervention. Anthropometric parameters, body composition, cardiometabolic markers, and VO2max were assessed before and after the intervention. Targeted metabolomics of 30 amino acid-related metabolites was performed in the MHO-R (remained MHO) and MUO-C (conversion from MUO to MHO) groups to explore exercise-associated metabolic adaptations following intervention. Results: Exercise training improved cardiometabolic risk profiles, including reductions in adiposity and improvements in insulin resistance-related markers. A proportion of participants transitioned from metabolically unhealthy to metabolically healthy obesity following the intervention. No significant between-group differences in amino acid metabolite changes were observed between MHO-R and MUO-C groups. Exploratory metabolomic analyses identified exercise-responsive alterations in amino acid-related metabolites, particularly involving arginine biosynthesis and histidine metabolism. Conclusions: Combined aerobic and resistance training is associated with improvements in metabolic health and phenotype transition in young adults with obesity. Observed alterations in arginine and histidine metabolism may reflect metabolic adaptations to exercise rather than transition-specific or causal mechanisms underlying phenotype conversion.