Metabolomics-identified metabolites associated with body mass index and prospective weight gain among Mexican American women

Objective: Obesity is a metabolic disease. However, the underlying molecular mechanisms linking metabolic profiles and weight gain are largely unknown. Methods: Here, we used semi-targeted metabolomics to assay 156 metabolites selected from 25 key metabolic pathways in plasma samples from 300 non-smoking healthy women identified from Mano-A-Mano, the Mexican American Cohort study. The study subjects were randomly divided into two cohorts: training (N = 200) and testing (N = 100) cohorts. Linear regression and Cox proportional hazard regression were used to assess the effect of body mass index (BMI) at baseline on metabolite levels and the effects of metabolites on significant weight gain during a 5-year follow-up. Results: At baseline, we observed 7 metabolites significantly associated with BMI in both training and testing cohorts. They were Methyl succinate, Asparagine, Urate, Kynurenic acid, Glycine, Glutamic acid, and Serine. In further analysis, we identified 6 metabolites whose levels at baseline predicted significant weight gain during 5-year follow-up in both cohorts. They were Acetylcholine, Leucine, Hippuric acid, Acetylglycine, Urate, and Xanthine. Conclusions: The findings establish the baseline metabolic profiles for BMI, and suggest new metabolic targets for researchers attempting to understand the molecular mechanisms of weight gain and obesity.