固醇调节元件结合蛋白表达降低导致高脂饲养大鼠发生肥胖抵抗的研究  

Research on down-regulated expression of SREBP1c leading to obesity resistance of rats fed with high fat diet

作　　者：王辉[1] 丁婧[1] 余诗灏[1] 孟雁[1] 

机构地区：[1]中国医学科学院基础医学研究所生理系,北京100005

出　　处：《临床荟萃》2010年第15期1289-1292,F0003,共5页Clinical Focus

基　　金：科技部重大基础研究前期研究专项(2004CCA01400);973项目(2006CB503907);国家自然科学基金(30870989);北京市自然科学基金(5062034)

摘　　要：目的研究肥胖抵抗大鼠与肥胖大鼠在肝脏脂代谢调控方面的差异。方法①55只4周龄雄性SD大鼠,无特定病原体(specific pathogen free,SPF)饲养环境下随机选取45只大鼠采用高脂饲料饲喂25周,根据体质量筛选得到饮食诱导的肥胖抵抗(diet-induced obesity resistance,DIO-R)大鼠与饮食诱导的肥胖(diet-induced obesity,DIO)大鼠,另10只大鼠采用基础饲料饲喂25周得到正常对照组大鼠。②用实时荧光定量聚合酶链反应(PCR)方法检测大鼠肝脏脂代谢调控基因固醇调节元件结合蛋白1c(sterol response element-binding protein1c,SREBP1c),碳水化合物反应元件结合蛋白(carbohydrate response element binding protein,ChREBP),肝脏X受体α(liver Xreceptorα,LXRα)及脂代谢相关酶类基因脂肪酸合酶(fatty acid synthase,FAS),乙酰辅酶A羧化酶(acetyl CoA carboxylase,ACC),肝型肉碱棕榈酰转移酶1(liver carnitine pal mitoyl transferase1,L-CPT1),二酰基甘油酰基转移酶(diacylglycerol acyltransferase,DGAT)mRNA的表达。③酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测大鼠血清胰岛素的含量。④苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察肝脏组织。结果饲养25周时,DIO-R组大鼠肝脏基因mRNA表达水平SREBP1c、FAS、ACC的中位数和(四分位数间距)分别为1.08(0.12)、1.44(0.53)、1.68(0.51)与DIO组大鼠3.65(1.19)、2.09(1.05)、2.07(1.01)相比明显降低(P<0.05或<0.01);DIO-R组大鼠的血清胰岛素水平M(QR)为0.56(0.19)μg/L显著低于DIO组大鼠0.85(0.37)(P<0.01);肥胖抵抗大鼠与肥胖大鼠都有脂肪变性。结论 DIO-R大鼠与DIO大鼠之间脂代谢调控区别主要由血浆胰岛素介导的SREBP1c的表达差异造成。Objective To study the liver lipid metabolism differences between obesity-resistant rats and obesity rats.Methods ①45 randomly selection included 55 male SD rats,4-week old,who were fed with high fat diet for 25 weeks under specific pathogen free environment.According to body mass difference,we got obesity-resistant rats and obesity rats.Another 10 rats were fed with basic diet for 25 weeks as normal control rats.②The mRNA expression of regulatory genes of lipid metabolism in rat liver：Serol response element-binding protein 1 c（SREBP1c）,carbohydrate response element binding protein（ChREBP）,liver X receptor α（LXRα） and lipid metabolism-related enzymes genes fatty acid synthase（FAS）,acetyl CoA carboxylase（ACC）,liver carnitine palmitoyl transferase 1（I-CPT1）,DGAT were detected by real-time PCR from five rats in each group.③The serum insulin level of normal control/DIO/DIO-R rats were measured by enzyme-linked immunosorbent assay.④Rat liver tissue in each group was sectioned and dyed with Hematoxylin-Eosin method for observation.Results At 25 weeks＇ feeding,the mRNA expression of SREBP1c,ACC,FAS as follows 1.08（0.12）,1.44（0.53）,1.68（0.51） were significantly lower （P〈0.05 or〈 0.01）,compared with DIO rats 3.65（1.19）,2.09（1.05）,2.07（1.01）.The serum insulin lever of DIO-R rats 0.56（0.19）,2.09（1.05）,2.07（1.01）.The serum insulin lever of DIO-R rats 0.56（0.19） μg/L was lower than DIO rats 0.85（0.37）（P〈0.05）.Meanwhile,there was fatty degeneration in both rats groups.Conclusion The differences in regulation of lipid metabolism between obesity-resistant rats and obesity rats are mainly caused by different expressions of SREBP1c,which may be mediated through plasma insulin.

关 键 词：脂代谢障碍 肥胖抵抗 基因调节 大鼠 

分 类 号：R589.2[医药卫生—内分泌]