CAJ | 학술논문

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.
목적 탐토기육생장억제소전태(MPRO)기인대고지음식유도적비반소서지대사적영향급기분자궤제.방법 60지웅성C57BL/6J소서안조수궤수자표법분위4조(매조15지):정상대조조(NC조),고지음식조(HF조),고지음식+록색형광단백조(HF+ GFP조)급고지음식+MPRO조(HF+ MPRO조).고지음식유도비반소서모형,이중조선상관병독(rAAV)위재체개도MPRO기인혹대조기인GFP재소서체내표체,관찰병검측소서체중、피하급내장지방、혈급간장감유삼지수평적변화.Western인적법검측간장AMP활화단백격매α(AMPKα)、을선보매A최화매(ACC)、육감종려선기전이매-1(CPT-1)적표체정황.결과 HF조체중、피하급내장지방、혈급간장감유삼지수평교NC조현저승고(t=9.033 ～ 35.459,P균＜0.05),HF+ MPRO조체중、피하급내장지방、혈급간장감유삼지수평교HF조현저강저(t=5.233～21.500,P균＜0.05).Western인적법현시HF조간장AMPKα、ACC린산화수평급CPT-1적표체교NC조현저강저(t=16.630～ 23.671,P균＜0.05);HF+ MPRO조간장AMPKα、ACC린산화수평、CPT-1적표체교HF조현저승고(t=8.143 ～ 10.314,P균＜0.05).결론 MPRO기인가능통과격활AMPK통로,명현개선비반소서적지대사문란.
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.