Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun, 130021, China.
Environ Sci Pollut Res Int. 2020 Feb;27(4):3837-3848. doi: 10.1007/s11356-019-06599-5. Epub 2019 Nov 15.
Exposure to di (2-ethylhexyl) phthalate (DEHP) induces lipid metabolism disorder and high-fat diet (HD) may have joint effects with DEHP. We aim to clarify the role of JAK2/STAT5 pathway in the process and reveal the effects of HD on the toxicity of DEHP. Wistar rats (160 animals) were fed with HD or normal diet (ND) respectively and exposed to DEHP 0, 5, 50, and 500 mg/kg/day for 8 weeks. Lipid levels, as well as the morphology of liver and adipose, mRNA levels, and protein levels of JAK2, STAT5A, STAT5B, FAS, ap2, and PDK4 were detected. The results showed that DEHP exposure leads to increased weight gain. The JAK2/STAT5 pathway was activated in adipose after DEHP exposure and promoted the expression of FAS, ap2, and PDK4 in ND rats. While in the liver, JAK2 was inhibited, and lipid synthesis and accumulation were increased. However, rats exposed to DEHP in combination with HD showed a complete disorder of lipid metabolism. Therefore, we conclude that DEHP affects lipid metabolism through regulating the JAK2/STAT5 pathway and promotes adipogenesis and lipid accumulation. High-fat diet may have a joint effect with DEHP on lipid metabolism disorder.
暴露于邻苯二甲酸二（2-乙基己基）酯（DEHP）会导致脂质代谢紊乱，而高脂肪饮食（HD）可能与 DEHP 具有联合作用。我们旨在阐明 JAK2/STAT5 通路在这一过程中的作用，并揭示 HD 对 DEHP 毒性的影响。将 Wistar 大鼠（160 只）分别用 HD 或正常饮食（ND）喂养，并分别暴露于 DEHP0、5、50 和 500mg/kg/天 8 周。检测脂质水平、肝和脂肪组织形态、JAK2、STAT5A、STAT5B、FAS、ap2 和 PDK4 的 mRNA 水平和蛋白水平。结果表明，DEHP 暴露会导致体重增加。DEHP 暴露后脂肪组织中 JAK2/STAT5 通路被激活，并促进 ND 大鼠中 FAS、ap2 和 PDK4 的表达。而在肝脏中，JAK2 受到抑制，脂质合成和积累增加。然而，同时暴露于 DEHP 和 HD 的大鼠表现出完全的脂质代谢紊乱。因此，我们得出结论，DEHP 通过调节 JAK2/STAT5 通路影响脂质代谢，促进脂肪生成和脂质积累。高脂肪饮食可能与 DEHP 对脂质代谢紊乱具有联合作用。
