Objective: To investigate the effect of peroxisome proliferation activated receptor-α(PPAR-α) activator on the fatty acid oxidation and the molecular mechanisms to improve high fat induced insulin resistance. Methods: Male SD rata were divided into 3 groups, group A (n=10): rats fed with saturated fatty acid,group B (n=10): rata fed with unsaturated fatty acid, group C (n=10): control rats. At the end of 4th weeks,the first 2 groups were divided into two groups: rats with or without Bezafibrate treatment. After another two weeks, blood samples were taken to detect fasting plasma glucose (FPG), fasting plasma insulin (FIN) and triglyceride (TG). The muscle, hepatic liver and adipose tissues were taken out from all the rats to assay the expression of PPAR-αand musle-type carnitine palmitoyltranferanse-1(CPT-1) mRNA by RT-PCR. Results:The expression of CPT-1 mRNA of musle and adipose tissues in no Bezafibrate treatment groups was lower than the Bezafibrate treatment groups and control but the expression of PPAR-αmRNA had no significant difference among all groups. Conclusions: The expression of CPT-1 mRNA is significantly decreased in high fat fed rats. PPAR-α activator bezafibrate can increase the expression of CPT-1. PPAR-α mRNA has no change in every group, suggesting that high fatty acid can suppress fatty acid β-oxidation and cause lipid accumulation and insulin resistance. PPAR-α activator can attenuate insulin resistance by increase fatty acid β-oxidation. This effect is not through suppress or promote the transcription of PPAR-α but as ligand to regulate fatty acid oxidation.%目的研究过氧化物酶增殖体激活受体α(peroxisome proliferation activated receptor-α,PPAR-α)激动剂对脂肪酸氧化的影响及其改善高脂诱导的胰岛素抵抗(IR)的机制.方法雄性SD大鼠随机分为三组(每组各10只),A组为饱和脂肪酸(1ard)组,B组为不饱和脂肪酸(soy)组,C组为正常对照组.大鼠饲养四周后将高脂饮食组各分为两组,高脂未干预组和苯扎贝特干预组.包头两周后检测空腹血糖、胰岛素和甘油三酯水平,并取出肝脏、肌肉和脂肪组织,检测组织肉碱脂酰转移酶-1(CPT-1)和PPAR-αmR-NA的表达,mRNA表达采用RT-PCR的方法,以β-actin作为内参照.结果肌肉和脂肪CPT-1mRNA表达在高脂未干预组明显低于苯扎贝物干预组和正常对照组,而未干预组间无显著差异.PPAR-αmRNA表达在各组间均无显著性差异.结论高脂饮食可使肌肉和脂肪组织CPT-1mRNA表达减少,而PPAR-αmR-NA激动剂苯扎贝特则可使CPT-1mRNA表达明显增加,肝脏PPAR-αmRNA表达在各组均无明显改变.这说明高脂饮食可能通过抑制脂肪酸β氧化导致组织细胞内脂质蓄积,最终造成IR,而用PPAR-α基因的抑制或促进作用,而是作为配体与PPAR-α受体结合对脂肪酸的氧化起调节作用.
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