运动对高脂饮食诱导肥胖大鼠过氧化物酶体增长因子活化受体-δ表达和胰岛素抵抗的影响

Effect of exercises training on expression of peroxisome proliferator-activated receptor-8 and insulin resistance in high fat diet induced obese rats

研究运动对高脂饮食诱导的肥胖大鼠肌肉和脂肪组织中过氧化物酶体增长因子活化受体-δ（PPAR-δ）表达的影响,并探讨其改善胰岛素抵抗的可能机制.方法 取体质量135～150 g的9周龄雄性Wistar大鼠80只,随机数字表法取其中60只6周时间饲以高脂饲料用于制作肥胖大鼠模型,另20只饲以普通饲料.将54只造模成功肥胖大鼠随机分为高脂饮食组（HFD）、高脂饮食同时运动组（E-HFD）、高脂饮食后运动组（HFD-E）,每组18只,同时从普通饲料饲养大鼠中随机选择16只作为正常饮食组（RD）.按文献标准对各组大鼠进行6周运动训练.检测比较各组游泳运动训练后体质量、肿瘤坏死因子（TNF）-α、瘦素、白细胞介素（IL）-1的水平以及空腹血糖、空腹胰岛素并计算胰岛素敏感指数（ISI）,采用实时定量聚合酶链反应（RT-PCR）检测肌肉和脂肪组织中PPAR-δ、葡萄糖转运蛋白（GLUT）-4、磷酸肌醇3激酶（PI3K）mRNA的表达,并采用Western blot法检测肌肉和脂肪组织中PPAR-δ蛋白的表达水平.组间数据比较采用双侧t检验.结果 HFD组ISI为1.13±0.21,相比HFD组,E-HFD组和HFD-E组的IS1分别提高了 71.1%和45.7%（分别为2.09±0.32和1.80±0.34）,而HFD-E组低于E-HFD组,差异均有统计学意义（均P＜0.05）.HFD组TNF-α水平为（101±24）ng/L,相比HFD组,E-HFD组和HFD-E组则分别下降了20.0%和9.2%[分别为（81±16）和（92±19）ng/L],差异均有统计学意义（P＜0.05）.与HFD组相比,E-HFD组和HFD-E组瘦素和IL-I水平均有显著下降（均P＜0.05）.与HFD组相比,E-HFD组和HFD-E组骨骼肌和脂肪中PPAR-δ、GLUT-4、PI3K mRNA的表达均显著升高,差异均有统计学意义（均P＜0.05）,且在E-HFD组变化尤为显著（均P＜0.01）.与HFD组相比,E-HFD组骨骼肌和脂肪组织中PPAR-δ蛋白表达分别升高了388.4%和203.2%（均P＜0.05）;HFD-E组骨骼肌和脂肪组织中PPAR-δ蛋白的表达则分别升高了272.9%和117.9%（均P＜0.05）.结论 运动降低了高脂饮食诱导的肥胖大鼠的血清脂肪因子瘦素、TNF-α和IL-1水平,改善了胰岛素抵抗,可能是通过上调肌肉和脂肪组织中PPAR-δ的表达发挥作用.

Objective To investigate the effect of exercise training on the expression of peroxisome proliferator-activated receptor （PPAR）-δ in muscle and adipose tissue in high fat diet induced obese rats and to explore the possible mechanism of improving insulin resistance. Methods Sixty male nine-week old Wistar rats with a weight of 135 to 150 g were randomly selected by using random number table for production of obese rats models with high fat diet for 6 weeks,another 20 rats were fed with ordinary feed as control. A total of 54 rat models were established successfully and were divided randomly into three groups：high-fat diet group （HFD）,high fat diet whilst exercise group （E-HFD）,exercise after high fat diet group （HFD-E）,18 rats in each group; and 16 rats with ordinary diet were set as control： the normal diet group （RD）. The rats in all groups were given exercise training for 6 weeks according to the methods from literature. After the exercise training was done,the body weight,levels of tumor necrosis factor（TNF）-α,leptin,interleukin（IL）-1,fasting glucose,fasting insulin,insulin sensitivity index （ISI） and expression of PPAR-δ,GLUT-4,PI3K mRNA and PPAR-δ protein in muscle and adipose tissue in the groups were investigated and compared. Two-side t test was used in the comparison of data between the groups. Results The ISI in group HFD,E-HFD and HFD-E was 1. 13 ±0.21,2.09 ±0. 32 and 1. 80 ±0. 34,respectively;and it increased for 71.1% and 45.7% in group E-HFD and HFD-E compared to that in group HFD （ all P 〈 0. 05）. Compared with that in group HFD,the TNF-α level in group E-HFD and HFD-E decreased for 20. 0% and 9. 2% respectively （ （ 101 ± 24 ）ng/L,（81 ± 16 ） ng/L and （92 ± 19 ） ng/L,respectively） （ all P 〈 0. 05）. Compared to those in group HFD,the level of leptin and IL-1 in group E-HFD and HFD-E decreased significantly（ all P 〈 0. 05 ）. The expression level of PPAR-δ,GLUT-4,PI3K mRNA in muscle and fat tissue in group E-HFD and HFD-E increased significantly compared with those in group HFD,especially in group E-HFD（ all P 〈0. 05 ）. Compared with that in group HFD,the expression of PPAR-δ in muscle and fat tissues in group E-HFD increased for 388.4% and 203.2% ,respectively（ all P 〈0. 05 ）; and the expression of PPAR-δ in muscle and fat tissues in group E-HFD increased for 272. 9% and 117.9%,respectively（ all P 〈 0. 05 ）. Conclusion Exercise training improves insulin resistance and decreases the level of serum leptin,TNF-α and IL-I in high fat diet induced obese rat,and this effect is probably mediated by up-regulation of PPAR-δ.