Abstract 26: Plasma Metabolomic Profile of Adiposity in Childhood: Gen3G Study

Objective: Childhood obesity is associated with long-term adverse outcomes including increased risk of cardiometabolic diseases. The integration of metabolomics in determining metabolites specific to excess adiposity could identify novel markers of adverse adiposity accumulation and insights into the pathogenesis of obesity-related outcomes, but investigations in childhood are limited. Thus, our aim was to identify metabolite networks associated with adiposity in childhood using gold-standard measurements. Methods: This study used cross-sectional data from 329 children at mid-childhood (age 5.3 ± 0.3 years) from the Gen3G prospective pre-birth cohort. We quantified 1,038 plasma metabolites including 798 annotated and 240 unannotated molecules. We measured adiposity using the gold-standard dual-energy X-ray absorptiometry (DXA), as well as skinfold, waist circumference and body mass index (BMI). We applied weighted-correlation network analysis to identify networks of highly correlated metabolites. Spearman’s partial correlations were applied to determine the associations of adiposity measures with metabolite networks and individual metabolites, adjusting for age and sex, with false discovery rate correction. Results: We identified a network of 23 metabolites (MEmagenta on Figure), primarily comprised of lipids (primary and secondary bile acids metabolism sub-pathways), that showed positive correlations with DXA total and truncal fat (ρ adjusted = 0.11 to 0.19), skinfold measures (ρ adjusted = 0.09 to 0.26), and BMI and waist circumference (ρ adjusted = 0.15 and 0.18, respectively). Within this network, glycol-alpha-muricholate and glycol-beta-muricholate metabolites, bile acid sub-species associated with glucose and lipid metabolism, appeared to be driving the associations. These correlations remained consistent when stratified by sex. Conclusions: A unique network of metabolites was associated with adiposity measures at 5 years of age.