高脂喂养及罗格列酮干预对老年大鼠骨骼肌脂肪酸转位酶表达的影响

Effects of high-fat diets and rosiglitazone treatment on fatty acid translocase （FAT/CD36） expression in skeletal muscles of aged rat

目的观察高脂饮食对老年大鼠胰岛素抵抗（IR）和骨骼肌脂肪酸转位酶（FAT/CD36）表达的影响及罗格列酮的干预效果。方法21～23月龄Wistar大鼠60只随机分为对照组、高脂组（HF）、高脂＋罗格列酮干预组,并设4～5月龄Wistar大鼠20只作为青年对照组。清醒状态下,应用正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率评价胰岛素抵抗,实时荧光定量PCR和Western印迹技术检测骨骼肌组织FAT/CD36mRNA和蛋白表达变化。结果（1）喂养4周后,老年对照组与青年组比较及老年高脂组与老年对照组比较,空腹血糖、胰岛素、游离脂肪酸及血清、骨骼肌三酰甘油均明显升高,葡萄糖输注率下降,出现了胰岛素抵抗;（2）继续喂养4周后,高脂＋罗格列酮干预组空腹血糖、胰岛素、游离脂肪酸及血清、骨骼肌三酰甘油明显下降,葡萄糖输注率升高,胰岛素抵抗状态改善;（3）与青年组比较,老年对照组骨骼肌组织中的FAT/CD36表达升高（P〈0.01）,经高脂饮食喂养后FAT/CD36表达明显升高,罗格列酮干预治疗明显降低FAT/CD36表达（P〈0.01）。结论老龄和高脂饮食均可诱导大鼠IR并伴有骨骼肌组织FAT/CD36的表达增加,罗格列酮降低FAT/CD36的表达,可能是改善胰岛素抵抗的机制之一。

Objective To investigate the effects of high-fat diets on insulin resistance and the expression at protein and mRNA level of fatty acid translocase （FAT/CD36） in muscle tissue in aged rats. Methods Wistar rats aged 21-23 months were divided into aged control group, high-fat diet （HF） group and high fat diet plus rosiglitazone maleate （HF＋Rosi） group, and Wistar rats aged 4-5 months were selected as young group （n= 20 in each group）. Insulin sensitivity was evaluated by conscious hyperinsulinemic-euglycemic clamp techniques, the expression at protein and mRNA levels of FAT/CD36 in skeletal muscle were investigated by real time polymerase chain reaction （PCR） and Western blot methods. Results （1） The levels of fasting blood glucose, insulin and free fatty acid, plasma and muscle triglycerides in the aged control group and HF group were significantly higher and glucose infusion rate were significantly lower than those in the young control group and aged control group, respectively. The insulin resistance was induced successfully. （2） After another 4 weeks, the levels of fasting blood glucose, insulin and free fatty acid, plasma and muscle triglycerides in the HF＋ Rosi group were significantly lower and glucose infusion rate were significantly higher than those in the high-fat diet group. And insulin resistance in HF＋Rosi group were improved. （3） In skeletal muscle, the expression of FAT/CD36 increased in aged control group, compared with young group（P〈0.01）. Compared with the aged control group, the expression of FAT/CD36 increased in high-fat diet group. In HF＋ Rosi group, the expression of FAT/CD36 decreased significantly than that in HF group （P〈0.01）. Conclusions The aged rats fed high-fat diets develop insulin resistance with increased expression of FAT/CD36 in muscle, and a decreased expression of FAT/CD36 plays a pivotal role in insulin-sensitizing effect of rosiglitazone treatment, which may be one of the possible mechanism of improving insulin resistance.