骨骼肌腺苷酸活化蛋白激酶在高脂饮食诱导小鼠肥胖易感性差异中的作用

The Regulatory Role of pAMPKα2 in the Differential Susceptibility to High-fat Diet-induced Obesity

目的:通过观察高脂饮食诱导的肥胖倾向(DIO)及肥胖抵抗倾向(DIO-R)两种小鼠的血糖、血脂变化,探讨腺苷酸活化蛋白激酶活性水平在高脂饮食诱导小鼠肥胖易感性差异中的作用。方法:雄性ICR小鼠随机分为普通饮食对照组和高脂饮食组。喂养5周后,将高脂饮食组体重增加最大的10只判定为肥胖倾向小鼠,体重增加最小的10只判定为肥胖抵抗倾向小鼠。小鼠摘眼球取血后,检测血糖、血脂浓度。采用免疫印迹(Western Blot)法测定小鼠骨骼肌组织磷酸化的腺苷酸活化蛋白激酶α2(AMPKα2)、过氧化物酶增殖物激活受体γ共化合物1α(PGC-1α)、雌激素受体相关受体α(ERRα)和肉毒碱棕榈酰转移酶-1(CPT-1)蛋白表达。结果:(1)高脂饮食喂养5周后,DIO小鼠体重显著高于对照组和DIO-R小鼠(P<0.05)。(2)与普通饮食对照组小鼠相比,DIO小鼠和DIO-R小鼠血糖、血脂均有显著性差异(P<0.01),而DIO小鼠与DIO-R小鼠之间血脂四项无显著性差异。(3)高脂饮食喂养5周后,DIO小鼠骨骼肌pAMPKα2蛋白表达水平较普通饮食对照组显著减少(P<0.05)。结论:(1)对同一批小鼠采用同样高脂饮食喂养5周后,DIO和DIO-R小鼠体重增长显著不同,而血糖和血脂变化无明显差异。(2)在高脂饮食刺激下,小鼠骨骼肌AMPKα2活性差异可能导致骨骼肌内脂肪酸氧化水平不同,诱导出现DIO和DIO-R。

Objective To explore the regulatory role of pAMPKa.2 in the differential susceptibility to high-fat diet-induced obesity. Methods Male ICR mice were randomly divided into chow diet group and high -fat diet group. After 5 weeks, the heaviest 10 mice in high -fat diet group were considered to be high fat diet -induced obese （DIO ） and the remaining 10 mice to be high fat diet -induced obesity resistant（DIO-R）. Blood glucose and blood lipids were assayed. The expression of pAMPKa.2,PGC-1α, ERRa. and CPT1- M in skeletal muscle were detected by Western blot. Results （1） The increase of body weight in DIO mice was significantly greater than that in DIO-R mice and chow diet mice （P 〈 0.05）. （2）The levels of serum lipids were higher in both DIO and DIO-R groups compared with chow diet group P 〈 0.01）, while there was no difference in blood lipids between DIO and DIO-R mice. （3 ）The expression of pAMPKa2 significantly decreased in skeletal muscle in DIO mice after feeding five-week high-fat diet as compared with chow diet mice（P 〈 0.05）. Conclusions（1）The susceptibility to high-fat diet in the same lot of mice was significantly different in the increasing of body weight, and had no significant changes in the serum CHO,HDLC,LDLC and blood glucose levels. （2）The differential susceptibility to high-fat diet-induced obesity could be due to the different levels of AMPKa2 activation in skeletal muscle of mice.