邻苯二甲酸二(2-乙基)己酯暴露对雄性小鼠脂肪代谢的影响

The effects of diethylhexyl phthalate on lipid metabolism of male mice

目的探索邻苯二甲酸二(2-乙基)己酯(diethylhexyl phthalate, DEHP)是否通过影响脂肪分解过程促进肥胖发生。方法雄性C57小鼠随机分为6组,即对照组、0.05 mg/kg·bw DEHP组、500 mg/kg·bw DEHP组、高脂饲料喂养组(high fat diet, HFD)组、0.05 mg/kg·bw DEHP+HFD、500 mg/kg·bw DEHP+HFD组,每组12只,其中0.05 mg/kg·bw为人体日常暴露剂量,500 mg/kg·bw为能够明显引起肝和肾毒性的剂量。经口灌胃13周,观察不同膳食情况下DEHP对动物体重、体内脂肪含量、血清生化指标及脂肪代谢相关蛋白的影响。结果喂饲普通饲料情况下,与对照组相比,0.05 mg/kg·bw DEHP能明显增加动物体重(P<0.05),增加肝和脾重量(P<0.05),升高体内白色脂肪、降低棕色脂肪(P<0.05);500 mg/kg·bw DEHP暴露能够明显增加小鼠肝重量,损伤肝功,表现为天冬氨酸转氨酶(AST)以及丙氨酸转氨酶(ALT)活性明显升高(P<0.01),同时增加肾重量(P<0.05)、降低睾丸重量(P<0.01)。与对照组相比,HFD喂养明显增加动物增重、体内脂肪,升高血脂水平(P<0.05、P<0.01),但与常规饲料喂养相比,HFD喂养联合DEHP染毒,对以上各指标的影响较小,差异无统计学意义(P>0.05)。Western blot结果显示,普通饲料喂养情况下,DEHP暴露明显降低脂肪组织解偶联蛋白1(UCP1)、蛋白激酶A(PKA)、激素敏感脂肪酶(HSL)的表达,以及HSL的磷酸化水平。结论 DEHP长期暴露导致雄性小鼠体重及体内白色脂肪增加、升高血脂、抑制脂肪分解,造成体内脂肪沉积,DEHP对HFD诱导雄性小鼠肥胖无促进作用。

Objective To explore whether diethylhexyl phthalate(DEHP) contributes to obesity by affecting the process of lipolysis. Methods Male C57 mice were randomly divided into 6 groups: control group, 0.05 mg/kg·bw DEHP group, 500 mg/kg·bw DEHP group, high fat diet(HFD) group, 0.05 mg/kg·bw DEHP+HFD, 500 mg/kg·bw DEHP+HFD group, 12 in each group. Among them, 0.05 mg/kg·bw is the daily exposure dose of human, and 500 mg/kg·bw is the dose that can obviously cause liver and kidney toxicity. Gavaged for 13 consecutive weeks, the effects of DEHP on body weight, body fat content, serum biochemical indexes and fat metabolism related proteins were observed. Result Compared with the control group, 0.05 mg/kg·bw DEHP could significantly increase the weight of animals(P<0.05), increase the weight of liver and spleen(P<0.05), increase the white fat and reduce the brown fat in the body(P<0.05), 500 mg/kg·bw DEHP exposure could significantly increase the weight of liver and damage the liver function of mice, which showed that the activities of transglutaminase and alanine aminotransferase were significantly increased(P<0.05). At the same time, kidney weight(P<0.05) and testis weight were increased(P<0.01). Compared with the control group, HFD feeding significantly increased animal body weight gain, body fat and blood lipid level(P<0.05), but compared with the standard chow diet, HFD feeding combined with DEHP poisoning had little effect on the above indicators. Western blot showed that DEHP exposure significantly reduced the expression of uncoupling protein 1(UCP1), protein kinase A(PKA), hormone sensitive lipase(HSL) and the phosphorylation level of HSL in the case of chow diet. Conclusion DEHP can increase the body weight and white fat, increase blood lipid, inhibit fat decomposition, and cause fat deposition in male mice. DEHP has no effect on the obesity of male mice induced by HFD.