Body Mass Index Modifies Associations Between Diet Quality and Circulating Metabolites: The CARDIA Study, 2005 to 2006

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BACKGROUND: Obesity perturbs metabolism, resulting in differential diet-disease associations, but metabolic pathways that differ by obesity remain unclear. We investigated whether cross-sectional associations between metabolites and diet quality differ by obesity status in 2832 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort study. METHODS: We used untargeted metabolomics (7255 metabolite peaks) and an a priori diet quality score (APDQS) to (1) compare model accuracy and prediction, stratified by body mass index (BMI); (2) assess modification of APDQS-metabolite associations by BMI in linear regression models; (3) identify pathways with differential metabolic activity by BMI; and (4) assess the strength and direction of associations with identified/annotated metabolites. RESULTS: =0.21). Of the 7255 metabolite peaks, 180 peaks were associated with APDQS and differed by BMI (false discovery rate<0.1). From pathway enrichment analyses, 6 pathways had differential metabolic activity by BMI (Fisher's exact test <0.05) including primary bile acid biosynthesis; steroid biosynthesis; steroid hormone biosynthesis; caffeine metabolism; valine, leucine, and isoleucine biosynthesis; linoleic acid metabolism. Strength of associations were strongest for those without overweight or obesity. CONCLUSIONS: Diet-metabolite associations were best detected among participants who did not have overweight/obesity. We identified associated diet-metabolic pathways that differ by obesity, suggesting potential metabolic-related mechanisms perturbed for those with obesity.

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