肌肉生长抑制素前肽基因干预对高脂饮食诱导的肥胖小鼠脂代谢的影响  

Effects of myostatin propeptide gene intervention on dyslipidemia in high fat diet-induced obese mice

作　　者：张莎莎[1,2] 孟杰杰 沈桂芬[4] 汪培华[1,2] 汪道文[1,2] 蒋建刚[1,2] 

机构地区：[1]华中科技大学同济医学院附属同济医院心血管内科,武汉430030 [2]高血压病研究所,武汉430030 [3]沧州市人民医院心血管内二科,武汉430030 [4]华中科技大学同济医学院附属同济医院风湿免疫科, 武汉430030

出　　处：《国际内分泌代谢杂志》2014年第6期361-364,共4页International Journal of Endocrinology and Metabolism

基　　金：国家自然科学青年基金项目（30900694）;教育部留学服务中心回国基金项目（JYBHG201005）

摘　　要：目的 探讨肌肉生长抑制素前肽（MPRO）基因对高脂饮食诱导的肥胖小鼠脂代谢的影响及其分子机制.方法 60只雄性C57BL/6J小鼠按照随机数字表法分为4组（每组15只）：正常对照组（NC组）,高脂饮食组（HF组）,高脂饮食＋绿色荧光蛋白组（HF＋ GFP组）及高脂饮食＋MPRO组（HF＋ MPRO组）.高脂饮食诱导肥胖小鼠模型,以重组腺相关病毒（rAAV）为载体介导MPRO基因或对照基因GFP在小鼠体内表达,观察并检测小鼠体重、皮下及内脏脂肪、血及肝脏甘油三酯水平的变化.Western印迹法检测肝脏AMP活化蛋白激酶α（AMPKα）、乙酰辅酶A羧化酶（ACC）、肉碱棕榈酰基转移酶-1（CPT-1）的表达情况.结果 HF组体重、皮下及内脏脂肪、血及肝脏甘油三酯水平较NC组显著升高（t=9.033 ～ 35.459,P均＜0.05）,HF＋ MPRO组体重、皮下及内脏脂肪、血及肝脏甘油三酯水平较HF组显著降低（t=5.233～21.500,P均＜0.05）.Western印迹法显示HF组肝脏AMPKα、ACC磷酸化水平及CPT-1的表达较NC组显著降低（t=16.630～ 23.671,P均＜0.05）;HF＋ MPRO组肝脏AMPKα、ACC磷酸化水平、CPT-1的表达较HF组显著升高（t=8.143 ～ 10.314,P均＜0.05）.结论 MPRO基因可能通过激活AMPK通路,明显改善肥胖小鼠的脂代谢紊乱。Objective To investigate the effects and the associated molecular mechanism of myostatin propeptide （MPRO） gene intervention on dyslipidemia in high fat diet-induced obese mice.Methods Sixty C57BL/6J mice were divided into four groups according to the random number table （15 mice in each group）：normal control group （NC group）,high fat diet group （HF group）,high fat diet ＋ green fluorescent protein group （HF ＋ GFP group） and high fat diet ＋ MPRO group （HF ＋ MPRO group）.Mice were fed with high fat diet to induce obesity and dyslipidemia.Recombinant adeno-associated virus （rAAV） mediated MPRO or GFP gene were introduced to the mnice,and their body weight,subcutaneous and visceral fat,as well as triglyceride in plasma and liver were measured.The expression of AMP-activated protein kinase α （AMPKαα）,acetyl-CoA carboxylase （ACC） and carnitine palmitoyltransferase-1 （CPT-1） were detected by Western blot.Results Compared with NC group,body weight,subcutaneous and visceral fat,triglyceride in plasma and liver were significantly increased in HF group （t =9.033-35.459,all P 〈 0.05）.However,these were lower in HF ＋ MPRO group than those in HF group （t =5.233-21.500,all P 〈0.05）.Western blot demonstrated that compared with NC group,the phosphorylation of AMPKα and ACC as well as the expression of CPT-1 were lower in HF group （t =16.630-21.502,all P 〈 0.05）.However,these were higher in HF ＋ MPRO group than those in HF group （t =8.143-10.314,all P 〈 0.05）.Conclusion MPRO gene intervention attenuates dyslipidemia in obese mice partly through AMPK pathway.

关 键 词：肌肉生长抑制素前肽 肌肉生长抑制素 高脂饮食 肥胖 

分 类 号：R589.2[医药卫生—内分泌]