二甲双胍对OLETF大鼠不同部位脂肪分解的影响  

Effects of metformin on lipolysis in different fat depots of OLETF rat

作　　者：李昂[1] 张婷婷[1] 张俊清[1] 姚军[1] 郭晓蕙[1] 

机构地区：[1]北京大学第一医院内分泌科,北京100034

出　　处：《中国临床药理学杂志》2013年第6期449-452,456,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81000347)

摘　　要：目的观察二甲双胍对OLETF大鼠附睾和皮下脂肪分解速率的影响及其可能机制。方法 OLETF大鼠8周时随机分为模型组和实验组,以同品系LE-TO大鼠为正常对照,在8,28周龄时分别行口服葡萄糖耐量试验(OGTT)及空腹胰岛素测定,测皮下及附睾脂肪组织重量及甘油释放量,用Western blot法检测腺苷酸激活蛋白激酶(AMPK)及其Thr-172磷酸化形式(pThr172-AMPK)的蛋白表达。结果 28周时模型组OGTT 1,2 h血糖、空腹胰岛素水平均明显高于正常组,实验组上述指标明显低于模型组;28周时正常组及实验组附睾脂肪组织甘油释放量明显高于皮下,模型组未见部位间差异;实验组皮下脂肪组织pThr172-AMPK蛋白表达明显高于附睾脂肪组织。结论胰岛素抵抗时OLETF大鼠丧失部位间脂肪分解速率的差异;二甲双胍通过选择性影响不同部位脂肪组织AMPK磷酸化,可以恢复附睾脂肪相对较高的脂肪分解速率。Objective To observe the effects of metformin on lipolysis in epididymal and subcutaneous fat depots of OLETF rats and to explore possible molecular mechanism involved.Methods OLETF rats were randomized to receive metformin（experimental） or placebo（model） at the age of 8 weeks,and LETO rats were used as age-matched normal controls.All the rats underwent oral glucose tolerance tests（OGTT） and fasting insulin measurement at the age of 8 weeks and 28 weeks.The rats were sacrificed to obtain abdominal subcutaneous adipose tissue（SAT） and epididymal adipose tissue（EAT） in corresponding weeks.Weight of tissues and glycerol released in the culture medium was measured respectively.The protein levels of AMP-activated protein kinase（AMPK） and its phosphorylated form（pThr172-AMPK） were examined by western blot assay.Results Body weight,the ratio of SAT to body weight and the ratio of EAT to body weight of model group were all higher than these of control group at the age of 28 weeks,but no significant difference was observed between experimental and model group in these parameters.The plasma glucose level of OGTT 1h,OGTT 2 h and fasting insulin level of model group were all higher than these of control group and experimental group at the age of 28 weeks,respectively.Glycerol released from EAT was higher than SAT in control and experimental group at the age of 28 weeks,respectively.No difference between glycerol released from SAT and EAT in model group at the age of 28 weeks was found.In experimental group,pThr172-AMPK protein expression of SAT was increased compared with EAT.Conclusion OLETF rat lost the differences on lipolysis rate between SAT and EAT in insulin resistance state.Compare to SAT,metformin could restored higher lipolysis rate in EAT by its depot-specific effects on AMPK phosphorylation.

关 键 词：OLETF大鼠 二甲双胍 脂肪分解 腺苷酸激活蛋白激酶 

分 类 号：R977.11[医药卫生—药品] R965.1[医药卫生—药学]