Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
Department of Bioinformatics and Biostatistics, University of Louisville School of Public Health and Information Sciences, Louisville, KY, USA.
Sci Rep. 2019 Oct 11;9(1):14675. doi: 10.1038/s41598-019-50771-3.
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.
暴露于环境毒物镉 (Cd) 会导致与肥胖相关的疾病的发展。肥胖是一系列不健康状况的风险因素,包括全身代谢失调。在本研究中,研究了一生中暴露于与环境相关浓度的 Cd 对高脂肪饮食 (HFD) 喂养的成年小鼠全身必需金属分布的影响。对于这些研究,雄性和雌性小鼠在繁殖前用含 Cd 的饮用水暴露超过 2 周。怀孕的老鼠和有后代的母鼠用含 Cd 的饮用水暴露。断奶后,后代继续暴露于与父母相同的 Cd 浓度,并分为 HFD 和正常(低)脂肪饮食 (LFD) 组。在 10 和 24 周时,处死小鼠并采集血液、肝脏、肾脏和心脏进行金属分析。在肾脏>肝脏>心脏中,Cd 水平随浓度的增加呈显著的依赖性增加。性别显著影响肾脏和肝脏中的 Cd 水平,雌性动物比雄性动物积累更多的金属。与接受相同处理的 LFD 小鼠相比,HFD 喂养的小鼠在这三个器官中的 Cd 水平增加了两倍以上。Cd 显著影响血液、肾脏和肝脏中必需金属的水平。此外,HFD 还影响这三个器官中的必需金属水平。这些发现表明,Cd 与 HFD 相互作用会影响必需金属的动态平衡,这种现象可能是导致肥胖相关病理发展的潜在机制之一。