Metabolomic correlates of central adiposity and earlier life body mass index

Body mass index (BMI) is correlated with circulating metabolites but few studies discuss other adiposity measures and little is known about metabolomic correlates of body mass index from early life. We investigated associations between different adiposity measures, BMI from childhood through adulthood, and metabolites quantified from serum using 1H NMR spectroscopy in 900 British men and women aged 60-64. We assessed BMI, waist-to-hip ratio (WHR), and android-to-gynoid fat ratio (AGR) and BMI from childhood through adulthood. Linear regression with Bonferroni adjustment was performed to assess adiposity and metabolites. Of 233 metabolites, 168, 126, and 133 were associated with BMI, WHR and AGR at age 60-64, respectively. Associations were strongest for high density lipoprotein (HDL), particularly HDL particle size, e.g. there was 0.08 SD decrease in HDL diameter (95% CI: 0.07-0.10) with each unit increase in BMI. BMI-adjusted AGR or WHR were associated with 31 metabolites where there was no metabolome-wide association with BMI. We identified inverse associations between BMI at age 7 and glucose or glycoprotein at age 60-64 and relative large LDL cholesterol ester with post-adolescent BMI gains. In summary, we identified metabolomic correlates of central adiposity and earlier life BMI. These findings support opportunities to leverage metabolomics in early prevention of cardiovascular risk attributable to body fatness