DEHP and DINP Induce Tissue- and Gender-Specific Disturbances in Fatty Acid and Lipidomic Profiles in Neonatal Mice: A Comparative Study

作者：Yichao Huang, Fengjiang Sun, Hongli Tan, Yongfeng Deng, Zhiqiang Sun, Hexia Chen, Jing Li, Da Chen · 发表于：Environmental Science & Technology · 年份：2019 · DOI：10.1021/acs.est.9b04369 · 被引用次数：81 · 研究领域：Effects and risks of endocrine disrupting chemicals、Fatty Acid Research and Health、Diet and metabolism studies

Di-isononyl phthalate (DINP) is considered one of the main industrial alternatives to di(2-ethylhexyl)phthalate (DEHP), a well-known chemical with various toxic effects including the disruption with lipid metabolism. However, the potential effects of DINP on lipid metabolism have rarely been investigated in mammals. Our study demonstrated that exposure of neonatal mice to DEHP and DINP at a daily dose of 0.048 or 4.8 mg/kg from postnatal day 0 (PND0) to PND21 caused nonmonotonic as well as tissue- and gender-specific alterations of total fatty acid (FA) compositions in plasma, heart, and adipose tissues. However, the patterns of disruption differed between DEHP- and DINP-treated groups. On the basis of targeted lipidomic analyses, we further identified gender-specific alterations of eight lipid classes in plasma following DEHP or DINP exposure. At the higher dose, DEHP induced decreases in total phosphatidylcholines and phosphatidylinositol (PI) in females and increases in phosphatidylethanolamines (PEs) and triglycerides in males. By contrast, DINP at the higher dose caused alterations of PEs, PIs, phosphatidylserines, and cholesterols exclusively in male mice, but no changes were observed in female pups. Although the most significant dysregulation of lipid metabolism was often observed for the higher dose, the lower one could also disrupt lipid profiles and sometimes its effects may even be more significant than those induced by the higher dose. Our study for the first time...