The Effect Of DEHP On The Lipid Metabolism And Blood Pressure In Rats Fed With High-fat Diet

Di-(2-ethylhexyl)phthalate(DEHP),a widely used plasticizer,enters into human body via food,water,inhalation and skin contact.Studies demonstrated that DEHP exposure is related to abnormality of lipid metabolism and blood pressure.Obesity,as a important risk factor of cardiovascular disease,could also disturb lipid metabolism and blood pressure.In this study,an intragastrical administration method was adopted to evaluate the effect of DEHP on the lipid metabolism and blood pressure in rats fed with high-fat diet(HFD).In current study,thirty male Wistar rats were randomly divided into 5 groups.Rats in control group were fed with regular chow,while rats of the other 4 groups were fed with high-fat chow and were treated with different concentrations of DEHP(0,10,100 and 300mg/kg body weight/day)for 5 weeks by gavage.In order to evaluate the effect of DEHP on lipid metabolism,the levels of blood lipids were measured.In addition,reverse transcriptase-polymerase chain reaction(RT-PCR)and Western blot techniques were adopted to measure the expression of gene mRNA and protein levels.The result showed:(1)Body weight of rats wasn't significantly changed by DEHP.DEHP at the dose of 300mg/kg resulted in the significant decrease in Lee's index,waist circumference and epididymis adipose mass,and markedly increased the organ/body weight ratio of liver or kidney.(2)Compared with HFD group,10 mg/kg DEHP significantly elevated the TG,TC and LDL-C levels in HFD rats,but the mRNA or protein levels weren't changed significantly.(3)When compared to HFD group,100 mg/kg DEHP exposure elevated the level of LDL-C,while PPAR-?,CPT-1,SREBP-1c mRNA and FAS protein were also significantly up-regulated.(4)When HFD rats exposured to 300 mg/kg DEHP,the levels of TG and leptin mRNA were notably reduced.Also the levels of CPT-1,PPAR-? mRNA were markedly increased.Instead,leptin mRNA were markedly decreased.In addition,protein level of p-AMPK was elevated and decreased significantly,respectively.In order to evaluate the effect of DEHP on blood pressure,the pathway of reninangiot-ensin-aldosterone was studied.The result showed:(1)Compared with control,the blood pressure of HFD group was elevated,ACE and AT1 R mRNA levels were significantly up-regulated.(2)Compared with HFD group,10 mg/kg DEHP exposure decreased blood pressure and the levels of ACE and AT1 R mRNA,but increased the levelof Mas1 mRNA.(3)Compared with HFD,100mg/kg DEHP exposure resulted in the decrease of blood presure,and the levels of ACE and AT1 R mRNA were significantly reduced,while the level of Mas1 was obviously elevated.(4)When exposure to 300mg/kg DEHP,compared with the HFD group,blood presure was decreased,the mRNA and protein of ACE and AT1 R mRNA levels were down-regulated.In summary,DEHP at dose of 10 mg/kg might increase lipid synthesis,but this process may not be regulated by the AMPK signaling pathway.100 mg/kg DEHP might promotedthe lipid decomposition and synthesis simultaneously,and other signaling pathway may also be involved in this process.300 mg/kg DEHP exposure might promote lipid decomposition by activating AMPK signaling pathway.10 mg/kg DEHP exposure might decrease blood presuure by weakning ACE-Ang?-AT1 R signaling pathway.100mg/kg DEHP might decrease blood presuure by weakning ACE-Ang?-AT1 R signaling pathway and strengthening ACE2-Ang-(1-7)-Mas signaling pathway.300 mg/kg DEHP might lower blood pressure by inhibiting ACE2-Ang-(1-7)-Mas signaling pathway.