Cadmium Exposure Increases the Risk of Juvenile Obesity: A Human and Zebrafish Comparative Study

Abstract

OBJECTIVEHuman obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and a zebrafish model of adipogenesis.DESIGNAn extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) were analyzed for the presence Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age five years. Next, the role of Cd as a potential obesogen was analyzed in anin vivozebrafish model.RESULTSOur analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.CONCLUSIONOur findings identify Cd as potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.