Sex differences in response to a short-term training program intervention in obese adolescents: a plasma metabolomics study

BACKGROUND: This study aims to investigate sex differences in the response to short-term Training Program intervention and the underlying metabolomic mechanisms among obese adolescents. METHODS: A total of 98 obese adolescents underwent a 4-week, strictly controlled short-term Training Program intervention. Pre- and post-intervention measurements included body morphometry, body composition, lipid metabolism, and glucose homeostasis indicators. Plasma samples were analyzed using targeted metabolomics. Linear mixed-effects models (LMM) were employed to identify Sex-differential Responsive Metabolites, with volcano plots utilized to visualize metabolic regulation preferences between sexes. Hierarchical clustering analysis identified co-regulated metabolic modules within the Sex-differential Responsive Metabolites for pathway analysis. Partial least squares (PLS) regression models were constructed separately for males and females to identify metabolic biomarkers capable of predicting changes in clinical indicators. RESULTS: = 0.1853). CONCLUSIONS: Obese adolescents exhibit significant sexual dimorphism in their response to short-term Training Program. Under the same standardized training program, males achieve greater fat reduction and appear to leverage a synergistic strategy of fatty acid oxidation and protein sparing, whereas females prioritize amino-acid network fine-tuning. Predictive modeling indicates that sex-differential metabolites can predict glucolipid improvements in females. These findings provide a scientific basis for developing sex-differential exercise prescriptions for metabolic health.