Effects of di (2-ethylhexyl) phthalate and high-fat diet on lipid metabolism in rats by JAK2/STAT5
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.
KeywordsDEHP JAK2/STAT5 High-fat diet Lipid metabolism
Yuezhu Zhang, Lin Ye, and Liting Zhou designed the studies. Yuezhu Zhang, Liting Zhou, Zhaoming Zhang, and Qi Xu performed the experiments. Yuezhu Zhang and Lin Ye analyzed the data and prepared the manuscript. Qi Xu, Xu Han, Yaming Zhao, Xinyue Song, and Tianyang Zhao performed all the figures and tables and polished the language. All authors reviewed and approved the final manuscript.
This study was financially supported by the National Natural Science Foundation of China (grant no. 81573184) and the Plan B of the Bethune Medical Department of Jilin University (2018B12).
Compliance with ethical standards
The experimental protocol was approved by the Animal Use and Care Committee of Jilin University prior to the study, and the ethical approval code of the animal experiment is 2015-03-14.
Conflict of interest
The authors declare that they have no conflict of interest.
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