College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
Toxicol Lett. 2014 Mar 21;225(3):392-400. doi: 10.1016/j.toxlet.2014.01.006. Epub 2014 Jan 17.
We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice.
我们评估了 20 周慢性暴露于低剂量氯菊酯（CYP）、莠去津（ATZ）和 17α-乙炔雌二醇（EE2）对能量代谢的影响。在这里，雄性小鼠通过饮用水暴露于 50μg/kg BW/天 CYP、100μg/kg BW/天 ATZ 或 1μg/kg BW/天 EE2，持续 20 周。在暴露期间，小鼠喂食高能量饮食（HD）。慢性接触 EDC 不会显著影响体重，但 ATZ 和 CYP-HD 组的血清游离脂肪酸（FFA）水平、肝脂质积累和三酰甘油（TG）含量显著增加。为了确定涉及的机制，我们测定了肝和脂肪组织中葡萄糖和脂肪代谢途径中基因的表达水平。结果表明，慢性暴露于 ATZ 和 CYP 增加了参与从头 FFA 合成途径和 FFA 从血液转运的许多关键基因的 mRNA 水平。增加的 FFA 量通过线粒体中的β-氧化部分被消耗为能量。一些 FFA 通过上调主要基因在肝脏中合成 TG，导致 TG 水平和脂质积累增加。结果表明，慢性接触 EDC 有可能导致小鼠能量代谢失调和肝毒性。
