Lee Eui-Jin, Hong Yeon-Pyo, Yang Yun-Jung
Institute for Catholic Integrative Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea.
Department of Preventive Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Environ Anal Health Toxicol. 2024 Mar;39(1):e2024007-0. doi: 10.5620/eaht.2024007. Epub 2024 Mar 21.
Di(2-ethylhexyl)phthalate (DEHP) is commonly used to increase the flexibility of plastics. In our previous study, DEHP may increase hepatic lipid accumulation through modulating of acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) expression. Nevertheless, it is hard to understand the association between DEHP and DGAT1 in the liver because only one dosage of DEHP was used. Thus, this study performed to investigate the role of DGAT1 on hepatic lipid metabolism after various dosages of DEHP exposure. Four-week-old male Sprague-Dawley rats (n = 5/group) were administered corn oil (vehicle) or DEHP (0.75, 7.5, 15, or 150 mg/kg/day) once daily for seven days. DEHP 150 mg/kg/day treated group increased body weight gain and relative liver weight compared to the control (P = 0.044 and P = 0.049, respectively). In histological observation, elevation of hepatic lipid accumulation was observed in all DEHP-treated groups, except DEHP 150 mg/kg/day, compared to that in the control (all P < 0.001). Portal inflammatory infiltration and acidophilic bodies were observed in the liver at DEHP 7.5 mg/kg/day and above treated groups. In addition, malondiadehyde levels, a marker of lipid peroxidation, in the liver were increased in DEHP 7.5, 15 and 150 mg/kg/day compared to the control (P = 0.017, P = 0.001, and P = 0.002, respectively). The expression of Dgat1 in the liver was significantly increased in DEHP 7.5, 15 and 150 mg/kg/day compared to the control group (P = 0.019, P = 0.002, and P < 0.001, respectively); however, there were no significant changes in the protein levels. Therefore, excessive oxidative stress caused by DEHP may induce liver damage such as inflammation rather than hepatic lipid accumulation by regulating DGAT1 transcription.
邻苯二甲酸二(2-乙基己基)酯(DEHP)常用于增加塑料的柔韧性。在我们之前的研究中,DEHP可能通过调节酰基辅酶A:二酰甘油酰基转移酶1(DGAT1)的表达来增加肝脏脂质蓄积。然而,由于仅使用了一种剂量的DEHP,很难理解DEHP与肝脏中DGAT1之间的关联。因此,本研究旨在探讨不同剂量DEHP暴露后DGAT1在肝脏脂质代谢中的作用。四周龄雄性Sprague-Dawley大鼠(每组n = 5)连续七天每天一次给予玉米油(赋形剂)或DEHP(0.75、7.5、15或150 mg/kg/天)。与对照组相比,DEHP 150 mg/kg/天处理组的体重增加和相对肝脏重量增加(分别为P = 0.044和P = 0.049)。组织学观察发现,与对照组相比,除DEHP 150 mg/kg/天处理组外,所有DEHP处理组的肝脏脂质蓄积均升高(所有P < 0.001)。在DEHP 7.5 mg/kg/天及以上处理组的肝脏中观察到门静脉炎症浸润和嗜酸性小体。此外,与对照组相比,DEHP 7.5、15和150 mg/kg/天处理组肝脏中脂质过氧化标志物丙二醛水平升高(分别为P = 0.017、P = 0.001和P = 0.002)。与对照组相比,DEHP 7.5、15和150 mg/kg/天处理组肝脏中Dgat1的表达显著增加(分别为P = 0.019、P = 0.002和P < 0.001);然而,蛋白质水平没有显著变化。因此,DEHP引起的过度氧化应激可能通过调节DGAT1转录诱导肝脏损伤如炎症,而非肝脏脂质蓄积。