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Life sciences · Journal article
European Journal of Internal Medicine · November 1, 2026
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Background Clinical obesity is a systemic chronic disease, but its biological mechanisms, especially in the earlier stages of life, are elusive. We aimed to explore which circulating metabolites in adolescence were prospectively associated with the development of clinical obesity in young adulthood and to assess whether these associations differed by sex. Methods A prospective cohort study was conducted using data from the Avon Longitudinal Study of Parents and Children. Circulating metabolites were measured at 17 years of age with nuclear magnetic resonance spectroscopy. Clinical obesity was ascertained at 24 years of age. Multivariable logistic regression models were used to examine associations between each metabolite and clinical obesity. Independent associations of the identified metabolites were examined using a lagged exposure-wide approach. Findings In total, 3169 participants were included. After adjustment for potential confounders, nine metabolites were associated with clinical obesity, all of which remained significant after false discovery rate correction: apolipoprotein B; fatty acids; monounsaturated fatty acids; linoleic acid; omega-6 fatty acids; polyunsaturated fatty acids; alanine; isoleucine; and glycoprotein acetyls. These metabolites were associated with clinical obesity independently of each other after applying the lagged exposure-wide approach. Two sex–metabolite interactions were identified. Isoleucine (OR per-SD 1.66, 95% CI 1.20–2.29) and valine (OR per-SD 1.47, 95% CI 1.08–2.0) were associated with increased risk of clinical obesity in women only. Conclusions We identified circulating metabolites in adolescence that were independently associated with subsequent clinical obesity. The associations of isoleucine and valine in women may suggest sex-specific metabolic pathways.