罗格列酮对肥胖大鼠骨骼肌脂质及其相关蛋白表达的影响

Effect of rosigllitazone on lipid content and expression of lipid droplets related proteins in skeletal muscle of obese rat

目的探讨罗格列酮对肥胖大鼠骨骼肌脂质含量和脂滴相关蛋白磷酸化周脂素和小凹蛋白-3表达的影响。方法建立肥胖大鼠模型并以罗格列酮进行干预,14周后测量体质量、身长,检测生化指标,并对其进行正葡萄糖-高胰岛素钳夹试验;处死大鼠后提取骨骼肌,生化方法检测骨骼肌脂质含量、Western blot检测骨骼肌脂滴相关蛋白的表达水平。结果肥胖大鼠骨骼肌细胞内脂质沉积明显增加、磷酸化周脂素和小凹蛋白-3分别较对照组增加42%和26%,与胰岛素抵抗相关,而罗格列酮干预后可以显著降低肥胖大鼠的骨骼肌脂质含量、增加胰岛素敏感性,上调磷酸化周脂素和小凹蛋白-3的表达水平。结论罗格列酮增加胰岛素敏感性,上调磷酸化周脂素和小凹蛋白-3的表达水平与格列酮类改善脂质溢出、调节脂滴脂质构成,直接下调DAG等反应性脂簇有关。

Objective To explore the effect of obesity on lipid and expression of lipid droplets related proteins in skeletal muscle,and to discuss the effect of rosiglitazone intervention on expression of lipid droplets related proteins in skeletal muscle. Methods The animal model was established with Wistar rats and after 14 weeks follow-up, their weights, body lengths, plasma biochemical parameters were measured and then hyperinsulinemic-euglycemic clamp to assess insulin sensitivity of rats was proceeded. Then, the rats were sacrificed for detecting the levels of skeletal muscle lipid and expressions of lipid related proteins. Skeletal muscle triglyc eride（TG） ,diacylglyeerol（DAG） were investigated by biochemical methods. The expressions of phosphorylated perilipin and caveolin-3 were measured by western blotting. Results In obese states,lipid content in skeletal muscle was increased as well as expression of lipid droplets related proteins phosphorylated perilipin and caveolin-3 upregulated by 42% and 26% ,which were associated with insulin sensitivity. Rosiglitazone can decrease lipid content and upregulate the expressions of phosphorylated perilipin and cave olin-3 in skeletal muscle of the obese rats, while the whole body had better insulin sensitivity. Conclusion Rosiglitazone can increase insulin sensitivity and upregulate the expressions of phosphorylated perilipin and caveolin-3 in skeletal muscle, which may be a defencing mechanism by downregulating lipid content especially DAG to protect skeletal muscle when there is lipid overspill.