Wnt信号通路在有氧运动改善高脂饮食诱导C57BL/6小鼠胰岛素抵抗中的作用

The Role of Wnt Signaling Pathways in Attenuating High-fat Diet Induced-Insulin Resistance in C57BL/6 Mice after Aerobic Exercise

目的:探讨有氧运动对C57BL/6小鼠骨骼肌Wnt信号通路的关键蛋白糖原合成激酶(GSK3β)磷酸化表达水平及其下游信号蛋白分子连环蛋白(β-catenin)磷酸化水平的影响及其与胰岛素抵抗(IR)的关系。方法:将4周龄雄性C57BL/6小鼠随机分为正常对照组(Con组)和胰岛素抵抗模型组(IR组),分别喂饲标准饲料和高脂饲料10周。建立IR模型后,再将IR组随机分为高脂饮食安静组(HC组)和高脂饮食运动组(HE组);Con组随机分为正常饮食安静组(NC)和正常饮食运动组(NE),随后运动组小鼠进行持续6周、75%VO2max强度的有氧跑台运动。6周训练结束后24小时,分别检测小鼠口服糖耐量试验(OGTT)和空腹血清胰岛素值(FINs);采用苏木精-伊红(HE)染色观察小鼠胰腺组织胰岛β细胞形态学变化;采用Realtime PCR及Western Blot方法检测小鼠骨骼肌GSK3β和β-catenin基因及蛋白表达。结果:(1)与NC组相比,HC组小鼠OGTT、FINs及胰岛β细胞形态学结果呈现IR的病理生理学变化,而6周有氧跑台运动(HE vs HC)可以显著改善OGTT、FINs及胰岛形态学变化;(2)与NC组相比,HC组骨骼肌组织GSK3βm RNA表达及p GSK3βSer9蛋白表达分别下降60%及1.19%(P<0.05)。β-catenin m RNA和pβ-catenin Ser33/37Thr41蛋白表达分别增加60%和19.23%(P<0.05);(3)与NC组相比,NE组骨骼肌组织GSK3βm RNA表达和GSK3β蛋白表达分别增加40.00%(P<0.05)和36.11%,β-catenin m RNA表达降低15.00%(P<0.05)。结论:6周有氧运动可显著改善高脂饮食诱导小鼠IR,其机制与Wnt信号通路活性变化相关。

Objective To investigate the influence of aerobic exercise on the high-fat diet induced- insulin resistance （IR）. Methods 4-week old male C57BL/6 mice were randomly divided into normal control group （Con, feeding standard diet） and insulin resistance group （IR,feeding high fat diet for 10 weeks）. Thereafter mice in group IR were regrouped to high fat diet control group （HC） and high fat diet exercise group （HE） ,and mice in group Con regrouped to normal chow diet sedentary control group （NC） and normal chow diet exercise group （NE）. Mice in the two exercise groups ran on a treadmilI 60 min per day at the intensity of 75% VO2max for 6 weeks. Fasting serum insulin level and oral glucose tolerance of the mice were tested after 6 weeks of the experiment. The morphological change in the beta cells of islet was observed and the expressions of glycogen synthase kinase 3β （GSK315） and 15-catenin in skeletal muscle were detected. Results （1）Symptoms of IR improved significantly after 6-week aerobic treadmill exercise in group HE. （2） Compared with group NC,the expression levels of GSK3β mRNA and GSK3β-Ser9 phosphorylated protein decreased by 60.00%（P 〈 0.05） and 1.19% ,respectively in group HC,while β-catenin mRNA level and pβ- cateninSer33/37TThr41 phosphorylated protein expression level increased by 60.00% and 19.23% （P 〈 0.05）, respectively. （3）Compared with group NC,the levels of GSK3β mRNA and GSK3β protein expression increased by 40.00% （P 〈 0.05） and 36.11% ,respectively in group NE,while β-catenin mRNA level decreased by 15.00%（P 〈 0.05）. Conclusion 6-weeks aerobic exercise significantly improves high-fat diet induced-insulin resistance of mice probably through the regulation of Wnt signaling pathways.