Exercise triggers integrated lipid, sphingolipid and purine metabolic alterations in midlife women.

BACKGROUND: Regular moderate physical activity helps prevent cardiometabolic diseases, yet the underlying molecular pathways, particularly in women in early to mid-adulthood, remain incompletely understood. Women aged 30-50 years undergo hormonal and metabolic transitions that may modify both cardiometabolic risk and responsiveness to exercise. This study investigated exercise-induced changes in serum metabolic signatures in women aged 30-50 years following 8 weeks of moderate-intensity aerobic training (MAT). METHOD: Thirty-nine healthy pre-menopause females (30-50 years) with a BMI of 26.5-33.5 kg/m2 completed an 8-week supervised moderate-intensity aerobic exercise program. Fasting blood samples were collected before and after the intervention. Serum targeted quantitative metabolic profiling and clinical traits were assessed. RESULTS: Univariate analysis revealed a coordinated post-exercise upregulation of dihydroceramides, glycosylceramides, ceramides, acylcarnitines (e.g., C14:2, C3-DC/C4-OH), diacylglycerols(DG 16:0_20:4, DG O-18:2_18:2),triacylglycerols, selected cholesterol esters (e.g., CE 20:3), cystine, and the nucleobase-related metabolite xanthine, alongside decreases in specific phosphatidylcholines species (PC O-30:2, PC O-28:0, PC O-30:0, PC 42:2, LPC 26:0), the amino acid serine, and CE 14:0,decrease in DG 18:1_18:1, CE 14:1, CE 14:0 and the amino acid-related metabolite cystine. Post-exercise correlation analysis identified distinct associations between metabolic profiles and clinical traits, with higher physical activity (metabolic equivalent of task, MET) positively linked to selected ceramide species (Cer d18:1/16:0, Cer d18:2/18:0). CONCLUSION: Moderate aerobic exercise in midlife women elicits a coordinated serum metabolomic response characterized by remodeling of lipid and sphingolipid pathways, increased fatty acid related mitochondrial handling, and elevated energy/redox turnover. The upregulation of dihydroceramides, glycosylceramides, ceramides, acylcarnitines, glycerolipids, cholesterol esters, and xanthine, together with reductions in specific phosphatidylcholines, cystine and serine, supports an exercise-induced "lipid sphingolipid energy stress" signature. Distinct associations of ceramide, glyceride, and purine species with MET, insulin indices, BMI, HDL, and catalase further suggest that these metabolites are promising candidate markers of exercise adaptation in midlife women.