Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals

Abstract

Exposure to the environmental toxicant cadmium (Cd) contributes to the development of obesity-associated diseases. Obesity is a risk factor for a spectrum of unhealthy conditions including systemic metabolic dyshomeostasis. In the present study, the effects of whole-life exposure to environmentally-relevant concentrations of Cd on systemic essential metal distribution in adult mice fed a high-fat diet (HFD) were examined. For these studies, male and female mice were exposed to Cd-containing drinking water for >2 weeks before breeding. Pregnant mice and dams with offspring were exposed to Cd-containing drinking water. After weaning, offspring were continuously exposed to the same Cd concentration as their parents, and divided into HFD and normal (low) fat diet (LFD) groups. At 10 and 24 weeks, mice were sacrificed and blood, liver, kidney and heart harvested for metal analyses. There were significant concentration dependent increases in Cd levels in offspring with kidney > liver > heart. Sex significantly affected Cd levels in kidney and liver, with female animals accumulating more metal than males. Mice fed the HFD showed > 2-fold increase in Cd levels in the three organs compared to similarly treated LFD mice. Cadmium significantly affected essential metals levels in blood, kidney and liver. Additionally, HFD affected essential metal levels in these three organs. These findings suggest that Cd interacts with HFD to affect essential metal homeostasis, a phenomenon that may contribute to the underlying mechanism responsible for the development of obesity-associated pathologies.

Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

“…1 ). Similar responses to HFD on cadmium accumulation were previously observed in hearts, kidneys and livers of the identical animals [ 43 ]. As with brain, female HFD-fed mice accumulated the highest level of metal in these tissues.…”

“…Female mice accumulated more cadmium than males, which was similar to that observed in other tissues [ 43 ]. Gender-specific differences in cadmium levels and several biological endpoints from blood, urine, liver and kidney have observed in several large human cohort studies [ 41 , 44 , 45 ].…”

“… * Details on the isolation and characteristics of heart, kidney and liver used in cadmium measurements can be found in [ 43 ]. …”

Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis

“…Cadmium and obesity interact to exacerbate human pathologies including prediabetes, metabolic syndrome and hypertension [ [24] , [25] , [26] ]. Additionally, in identical animals, HFD increases the levels of cadmium in the heart, liver, kidney and brain [ 8 , 9 ]. Therefore, the impact of HFD on cadmium levels in the testis was also examined.…”

“…Although the major sites for cadmium accumulation and storage in mammals are the kidney followed by the liver, recent studies show cadmium also accumulates in the heart and brain [ 8 , 9 ]. Analysis of human autopsy tissue report significant levels of cadmium in testis, epididymis, prostate and seminal vesicles, which increases as a function of age [ 10 ].…”