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Relationships between di-(2-ethylhexyl) phthalate exposure and lipid metabolism in adolescents: Human data and experimental rat model analyses
Environmental Pollution ( IF 8.9 ) Pub Date : 2021-06-15 , DOI: 10.1016/j.envpol.2021.117570
Shuang Ding 1 , Wen Qi 2 , Qi Xu 2 , Tianyang Zhao 2 , Xu Li 2 , Jianli Yin 2 , Ruxuan Zhang 2 , Chuanyi Huo 2 , Liting Zhou 2 , Lin Ye 2
Affiliation  

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16–19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3. Animal experiments were performed to confirm and expand findings. Wistar rats were administered DEHP at 0, 5, 50, and 500 mg/kg/d for 8 weeks. The serum and liver levels of TC, TG, HDL-C, and LDL-C, and the liver mRNA and protein levels of SREBP-2, SR-BI, LDLR, and NR1H3 were measured. The results showed that WHR, VAI, and LAP were significantly positively associated with the urinary levels of MECPP and ∑DEHP; the plasma HDL-C level was significantly negatively associated with the levels of MECPP, MCMHP and ∑DEHP; the peripheral blood leukocyte mRNA levels of SREBP-2, NR1H3, and LDLR were significantly positively correlated with the MCMHP level; and the SR-BI mRNA level was significantly positively correlated with the levels of MECPP and MCMHP in adolescents. Moreover, the results of animal experiments showed that DEHP exposure significantly increased the serum levels of TC, HDL-C, and LDL-C in 500 mg/kg/d group, as well as the liver levels of TC and HDL-C, up-regulated SREBP-2 mRNA and protein expression in 50 and 500 mg/kg/d groups. DEHP exposure significantly down-regulated SR-BI and NR1H3 protein expression in the liver of the 500 mg/kg/d group rats. Our findings indicate that DEHP exposure can affect lipid metabolism in adolescents by regulating the expression of lipid metabolism-related genes.



中文翻译:

青少年邻苯二甲酸二(2-乙基己基)酯暴露与脂质代谢之间的关系:人类数据和实验大鼠模型分析

近年来,青少年脂代谢紊乱的发病率逐渐升高,DEHP对脂代谢的影响受到广泛关注。在这项研究中,463 名 16-19 岁的青少年被纳入研究对象。本研究分析了尿中 DEHP 代谢物(MEHP、MEOHP、MEHHP、MECPP、MCMHP 和 ∑DEHP)水平与 BMI、WHR、WtHR、VAI、LAP、血脂水平(TC、TG、HDL- C 和 LDL-C),以及 SREBP-2、SR-BI、LDLR 和 NR1H3 的外周血白细胞 mRNA 水平。进行了动物实验以确认和扩大发现。Wistar 大鼠以 0、5、50 和 500 毫克/千克/天的剂量服用 DEHP,持续 8 周。测量血清和肝脏的 TC、TG、HDL-C 和 LDL-C 水平,以及肝脏 SREBP-2、SR-BI、LDLR 和 NR1H3 的 mRNA 和蛋白质水平。结果表明,WHR、VAI、LAP与尿中MECPP、∑DEHP水平呈显着正相关;血浆HDL-C水平与MECPP、MCMHP和∑DEHP水平显着负相关;SREBP-2、NR1H3、LDLR外周血白细胞mRNA水平与MCMHP水平呈显着正相关;SR-BI mRNA水平与青少年MECPP、MCMHP水平呈显着正相关。此外,动物实验结果表明,DEHP暴露显着增加500 mg/kg/d组血清TC、HDL-C和LDL-C水平,以及肝脏TC和HDL-C水平,在 50 和 500 mg/kg/d 组中 -调节 SREBP-2 mRNA 和蛋白质表达。DEHP 暴露显着下调 500 mg/kg/d 组大鼠肝脏中的 SR-BI 和 NR1H3 蛋白表达。我们的研究结果表明,DEHP 暴露可以通过调节脂质代谢相关基因的表达来影响青少年的脂质代谢。

更新日期:2021-06-15
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