邻苯二甲酸二乙基已酯对小鼠脂肪和葡萄糖代谢的影响
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摘要
目的探讨不同剂量的邻苯二甲酸二乙基已酯(DEHP)暴露对脂肪和葡萄糖代谢的影响。方法选用C57雄性小鼠40只,随机分为对照组和3个实验组,每组10只。3个实验组分别经灌胃给予0.05、5和500 mg/kg·bw的DEHP,连续4周。期间定期记录体重和饲料消耗情况,实验结束前进行葡萄糖耐量试验。实验结束,摘眼球取血,检测血糖及血脂;分离肝、棕色脂肪、腹壁脂肪和附睾脂肪,计算脏体比;肝油红O染色检测脂肪蓄积情况。结果实验期间,各组小鼠体重均呈增长趋势,其中500 mg/kg·bw DEHP组小鼠增重明显高于对照组(P<0.05);小鼠肝重量增加,肝脏系数明显高于对照组及其他2个剂量组(P<0.05)。3个DEHP染毒组小鼠腹壁脂肪重量增加,脏体比分别比对照组增加50.8%、36.3%和31.5%,与对照组比较差异有统计学意义(P<0.01)。其中0.05 mg/kg·bw组小鼠腹壁脂肪增加最为明显,但3个剂量组之间差异无统计学意义(P>0.05);各组小鼠附睾脂肪及棕色脂肪的脏体比差异无统计学意义(P>0.05)。葡萄糖耐量试验显示,500 mg/kg·bw组小鼠葡萄糖耐量受损,血糖曲线下面积明显高于对照组(P<0.05)。3个DEHP染毒组小鼠血脂水平均表现为升高趋势,5和500 mg/kg·bw DEHP组小鼠血清甘油三酯(TG)明显高于对照组(P<0.05);3个DEHP染毒组小鼠血清胆固醇(CHOL)、低密度脂蛋白(LDL)均明显高于对照组(P<0.01),0.05和5 mg/kg·bw DEHP组小鼠血清高密度脂蛋白(HDL-C)与对照组相比,差异有统计学意义(P<0.01)。肝病理组织切片的油红O染色结果显示DEHP染毒组肝脂肪蓄积,以500 mg/kg·bw组最为明显。结论一定剂量DEHP能够导致小鼠脂肪和葡萄糖代谢紊乱,增加肝和皮下脂肪蓄积。
Objective To investigate the effects of different doses of diethylhexyl phthalate(DEHP) on lipid and glucose metabolism. Methods Forty C57 male mice were randomly divided into control group and three experimental groups, with 10 mice in each group. The mice in three experimental groups were orally administered 0.05, 5 and 500 mg/kg·bw DEHP dissolved in corn oil for consective 4 weeks. Body weight and feed consumption were recorded periodically and glucose tolerance tests were performed. At the end of the experiment, blood taken from the eyeball was subjected to blood glucose and lipids detection. The liver and fat including brown fat, abdominal fat and epididymal fat were separated respectively, and the organ/body weight ratio was calculated. The oil red O staining was used to detect the fat accumulation in liver. Result During the experiment, the body weight in each group kept an steady increasing, the weight gain of mice in the 500 mg/kg·bw DEHP group was significantly higher than the control group(P<0.05). The liver weight of the mice in the 500 mg/kg·bw DEHP group increased and the liver coefficient was significantly higher than that of the control group and the other two dose groups(P<0.05). The fat weight and organ/weight ratio of the abdominal wall of the low, medium and high DEHP groups were significantly higher than those of the control group, which increased by 50.8%, 36.3% and 31.5%, respectively(P<0.01). There was no significant difference in the ogran/weight ratio of epididymal fat and brown fat in each group(P>0.05). The glucose tolerance test revealed that the 500 mg/kg·bw DEHP disturbed the glucose tolerance of mice, revealed by the significantly higher area under the blood glucose curve than control group(P<0.05). The DEHP treatment could increase the serum lipid of mice. The serum triglyceride(TG) of the 5, 500 mg/kg·bw DEHP group was significantly higher than that of the control group(P<0.05). The serum cholesterol(CHOL) and low density lipoprotein(LDL) of mice in 0.05, 5 and 500 mg/kg·bw DEHP group were significantly higher than the control group(P<0.01). The serum high-density lipoprotein(HDL-C) in the 0.05, 5 mg/kg·bw DEHP group was significantly different from that in the control group(P<0.01). The oil red O staining showed that DEHP-treatment could result in the liver fat accumulation, with obvious lipid droplet in the liver from 500 mg/kg·bw DEHP treated mice. Conclusion DEHP could lead to the glucose and lipid metabolism disorders in mice and increase liver and subcutaneous fat accumulation.
Objective To investigate the effects of different doses of diethylhexyl phthalate(DEHP) on lipid and glucose metabolism. Methods Forty C57 male mice were randomly divided into control group and three experimental groups, with 10 mice in each group. The mice in three experimental groups were orally administered 0.05, 5 and 500 mg/kg·bw DEHP dissolved in corn oil for consective 4 weeks. Body weight and feed consumption were recorded periodically and glucose tolerance tests were performed. At the end of the experiment, blood taken from the eyeball was subjected to blood glucose and lipids detection. The liver and fat including brown fat, abdominal fat and epididymal fat were separated respectively, and the organ/body weight ratio was calculated. The oil red O staining was used to detect the fat accumulation in liver. Result During the experiment, the body weight in each group kept an steady increasing, the weight gain of mice in the 500 mg/kg·bw DEHP group was significantly higher than the control group(P<0.05). The liver weight of the mice in the 500 mg/kg·bw DEHP group increased and the liver coefficient was significantly higher than that of the control group and the other two dose groups(P<0.05). The fat weight and organ/weight ratio of the abdominal wall of the low, medium and high DEHP groups were significantly higher than those of the control group, which increased by 50.8%, 36.3% and 31.5%, respectively(P<0.01). There was no significant difference in the ogran/weight ratio of epididymal fat and brown fat in each group(P>0.05). The glucose tolerance test revealed that the 500 mg/kg·bw DEHP disturbed the glucose tolerance of mice, revealed by the significantly higher area under the blood glucose curve than control group(P<0.05). The DEHP treatment could increase the serum lipid of mice. The serum triglyceride(TG) of the 5, 500 mg/kg·bw DEHP group was significantly higher than that of the control group(P<0.05). The serum cholesterol(CHOL) and low density lipoprotein(LDL) of mice in 0.05, 5 and 500 mg/kg·bw DEHP group were significantly higher than the control group(P<0.01). The serum high-density lipoprotein(HDL-C) in the 0.05, 5 mg/kg·bw DEHP group was significantly different from that in the control group(P<0.01). The oil red O staining showed that DEHP-treatment could result in the liver fat accumulation, with obvious lipid droplet in the liver from 500 mg/kg·bw DEHP treated mice. Conclusion DEHP could lead to the glucose and lipid metabolism disorders in mice and increase liver and subcutaneous fat accumulation.
引文
[1] 吴婷. 上海市社区老年高血压患者肥胖和超重现况调查[J]. 中国老年保健医学, 2018,16(2):71-72.
[2] Heinemeyer G, Sommerfeld C, Springer A, et al. Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population[J]. Int J Hyg Environ Health, 2013,216(4):472-480.
[3] Serrano SE, Braun J, Trasande L, et al. Phthalates and diet: a review of the food monitoring and epidemiology data[J]. Environ Health, 2014,13(1):43.
[4] Sun Q, Cornelis MC, Townsend MK, et al. Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses′ Health Study (NHS) and NHSII cohorts[J]. Environ Health Perspect, 2014,122(6):616-623.
[5] Zhao JF, Hsiao SH, Hsu MH, et al. Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice[J]. Arch Toxicol, 2016,90(1):181-190.
[6] Lv Z, Cheng J, Huang S, et al. DEHP induces obesity and hypothyroidism through both central and peripheral pathways in C3H/He mice[J]. Obesity (Silver Spring), 2016,24(2):368-378.
[7] Bae IS, Park PJ, Lee JH, et al. PPARgamma-mediated G-protein coupled receptor 120 signaling pathway promotes transcriptional activation of miR-143 in adipocytes[J]. Gene, 2017,626(1):64-69.
[8] Chiang HC, Wang CH, Yeh SC, et al. Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network[J]. Cell Biol Toxicol, 2017,33(6):511-526.
[9] Hao C, Cheng X, Xia H, et al. The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice[J]. Biosci Rep, 2012,32(6):619-629.
[10] Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene[J]. Embo J, 1996,15(19):5336-5348.
[11] Karavia EA, Papachristou NI, Sakellaropoulos GC, et al. Scavenger receptor class B type I regulates plasma apolipoprotein E levels and dietary lipid deposition to the liver[J]. Biochemistry, 2015,54(36):5605-5616.
[12] Im SS, Kwon SK, Kang SY, et al. Regulation of GLUT4 gene expression by SREBP-1c in adipocytes[J]. Biochem J, 2006,399(1):131-139.
[13] Rajesh P, Sathish S, Srinivasan C, et al. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins[J]. J Cell Biochem, 2013,114(3):558-569.
[14] Sun X, Lin Y, Huang Q, et al. Di(2-ethylhexyl) phthalate-induced apoptosis in rat INS-1 cells is dependent on activation of endoplasmic reticulum stress and suppression of antioxidant protection[J]. J Cell Mol Med, 2015,19(3):581-594.
[2] Heinemeyer G, Sommerfeld C, Springer A, et al. Estimation of dietary intake of bis(2-ethylhexyl)phthalate (DEHP) by consumption of food in the German population[J]. Int J Hyg Environ Health, 2013,216(4):472-480.
[3] Serrano SE, Braun J, Trasande L, et al. Phthalates and diet: a review of the food monitoring and epidemiology data[J]. Environ Health, 2014,13(1):43.
[4] Sun Q, Cornelis MC, Townsend MK, et al. Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses′ Health Study (NHS) and NHSII cohorts[J]. Environ Health Perspect, 2014,122(6):616-623.
[5] Zhao JF, Hsiao SH, Hsu MH, et al. Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice[J]. Arch Toxicol, 2016,90(1):181-190.
[6] Lv Z, Cheng J, Huang S, et al. DEHP induces obesity and hypothyroidism through both central and peripheral pathways in C3H/He mice[J]. Obesity (Silver Spring), 2016,24(2):368-378.
[7] Bae IS, Park PJ, Lee JH, et al. PPARgamma-mediated G-protein coupled receptor 120 signaling pathway promotes transcriptional activation of miR-143 in adipocytes[J]. Gene, 2017,626(1):64-69.
[8] Chiang HC, Wang CH, Yeh SC, et al. Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network[J]. Cell Biol Toxicol, 2017,33(6):511-526.
[9] Hao C, Cheng X, Xia H, et al. The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice[J]. Biosci Rep, 2012,32(6):619-629.
[10] Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene[J]. Embo J, 1996,15(19):5336-5348.
[11] Karavia EA, Papachristou NI, Sakellaropoulos GC, et al. Scavenger receptor class B type I regulates plasma apolipoprotein E levels and dietary lipid deposition to the liver[J]. Biochemistry, 2015,54(36):5605-5616.
[12] Im SS, Kwon SK, Kang SY, et al. Regulation of GLUT4 gene expression by SREBP-1c in adipocytes[J]. Biochem J, 2006,399(1):131-139.
[13] Rajesh P, Sathish S, Srinivasan C, et al. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins[J]. J Cell Biochem, 2013,114(3):558-569.
[14] Sun X, Lin Y, Huang Q, et al. Di(2-ethylhexyl) phthalate-induced apoptosis in rat INS-1 cells is dependent on activation of endoplasmic reticulum stress and suppression of antioxidant protection[J]. J Cell Mol Med, 2015,19(3):581-594.