Advance-CTR Pilot Projects Program (2020)
"Cord Metabolome and Childhood Obesity and Cardiometabolic Disease Risk"
Co-PI: Kurt Pennell, PhD
Childhood obesity and adverse cardiometabolic traits track from childhood into adulthood, increasing the risk of many chronic diseases such as heart disease, the leading cause of death in both the U.S. and Rhode Island. Environmental stressors (including external and internal factors) during fetal development may increase the risk of childhood obesity and cardiometabolic disease. These factors include macro- and micronutrients, endogenous metabolites, pharmaceuticals, and toxic chemicals and metals. Metabolomics is a promising tool to understand the etiology of obesity and cardiometabolic disease and predict those at greatest risk by measuring the metabolites from the diet, microbiome, environment, and endogenous metabolism, and link these to childhood obesity and cardiometabolic risk. Limited studies have investigated the fetal metabolome as a predictor of subsequent obesity and cardiometabolic risk. We will perform an untargeted high-resolution metabolomics analysis on previously collected cord blood in an ongoing cohort of ~200 mother-child pairs, the Health Outcomes and Measures of the Environment (HOME) Study. Our specific aims are: (1) to identify cord serum metabolites and metabolic pathways that are associated with childhood adiposity at age 12 years; (2) to identify cord serum metabolites and metabolic pathways that are associated with unfavorable childhood cardiometabolic risk profiles at age 12 years. Findings from this proposed study will greatly improve our understanding of early-life predictors of obesity and cardiometabolic disease, as well as underlying biological pathways. If we find that certain metabolites are early-life predictors of obesity and cardiometabolic diseases, and the findings are confirmed by other studies, there is the potential to reduce disease risk by intervening on identified metabolites via changes in diet, dietary supplements, chemical exposure, physical activity, or other lifestyle factors. This study provides multiple avenues for future research which would allow us to examine how serum metabolites at different time periods during fetal development and childhood influence children’s obesity and cardiometabolic risk and identify periods of susceptibility in the HOME Study and other cohorts. Ultimately, completion of this proposed study will demonstrate that Brown University can provide a platform to perform untargeted high-resolution metabolomics assays, which will facilitate future collaborations and allow us to continue developing this novel and promising line of research.