Cadmium exposure increases the risk of juvenile obesity: a human and zebrafish comparative study

Abstract

OBJECTIVE Human 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 in a zebrafish model of adipogenesis. DESIGN An extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) was analyzed for the presence of 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 an in vivo zebrafish model. RESULTS Our 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. CONCLUSION Our findings identify Cd as a 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.

RW‐2018—Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health

“…Therefore, one should confirm this in a model system, such the zebrafish model, because it is transparent and because accumulated lipid can be observed in real time. In zebrafish, cadmium but not lead exposure early in gestation significantly increased fatty deposits, similar to what was observed in children . This led to the conclusion that cadmium is indeed an obesogen.…”

“…These are markers for metabolic syndrome (type 2 diabetes mellitus, hypertension, obesity, and cardiovascular disease). However, human clinical studies have been inconsistent in demonstrating a clear link between cardiometabolic impairment/metabolic syndrome and cadmium exposure …”

“…Lead was associated with lower birth weight, accelerated growth in early childhood, and prehypertension. These are all early indicators of cardiometabolic syndrome in childhood …”

“…The specificity and accuracy increases if specific cell populations are targeted. When monocytes were targeted, a 14‐ to 15‐fold increase in methylation was observed after cigarette smoke exposure—a major source of cadmium exposure among smokers . The issue then becomes determining which genes should be examined for changes in methylation and whether there is an existing methylation profile to make comparisons to, so that exposures can be linked to shifts in the methylation profile.…”

Zebrafish as an Experimental Model for the Study of Obesity

“…As an example, there is a worrying fact that is gaining the attention of several researchers: the fact that obesity has a high prevalence in lower socioeconomic populations. Evidence shows that although genetic predisposition and a positive energy balance are implicated in obesity, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are widely suspected to have obesogenic activity, which are correlated with lower socioeconomic status [37,38].…”