The Toxic Effect of Environmental Cadmium on Visceral Adipose Tissue

Cadmium is an environmental toxin strongly associated with the development of cancer, kidney and liver disease, and bone demineralization. Whether cadmium causes obesity in humans remains a subject of controversy in the literature. An NHANES study that examined the effect of various toxic metals on central obesity demonstrated a decrease in the BMI of subjects exposed to cadmium. The purpose of this study is to examine the effect of cadmium on visceral adipose tissue (VAT), the potential for chelation to reverse cadmium‐induced changes, and to investigate the mechanism by which these changes occur. VAT is the subset of adipose tissue most heavily implicated in the pathogenesis of obesity, insulin resistance, and metabolic syndrome. ICR mice were placed into one of three groups: control, cadmium followed by washout, and cadmium followed by chelation. Mice in the two experimental groups were treated with 100ppm CdCl 2 drinking water for 8 weeks followed by either 8 weeks of washout or 8 weeks of chelation with DMSA. Digital analysis of H&E images was performed using ImageJ and morphometric parameters of approximately 400 adipocytes per group were obtained. A 14.6% reduction in adipocyte size was observed in the group treated with cadmium followed by washout relative to the control group (p < 0.0001). In the group that underwent chelation after cadmium exposure, there was an increase in adipocyte size relative to the cadmium‐washout group (p<0.002). Additionally, animals in the cadmium‐washout group had a 5% reduction in body weight relative to control (p<0.0001). There was no significant difference in weight between the control group and the cadmium‐chelation group. In conclusion, the mouse model we have developed demonstrates that chronic low dose cadmium exposure causes weight loss and that chelation has the potential to reverse this change. Although the effect of cadmium on body weight remains controversial, this mouse model may serve to clarify this relationship and address the mechanism of cadmium’s action. Support or Funding Information NIEHS Grant # P30 ES027792‐02