N-3PUFA降低肥胖型胰岛素抵抗大鼠血脂及提高胰岛素敏感性的机理研究

N-3PUFA regulate serum lipid metabolism and insulin sensitivity ,the effects are influenced by the types and quantities of n-3PUFA,but the mechanism is less clear.We pupose that different types and quantities of n-3PUFA may have various effects on gen expression involved in serum lipid metabolism and insulin resistance. Obesity-insulin resistant animal model induced by high fat diet is a significant tool for researching the molecular mechanism underlying alterations in the pathophysiologic status of dyslipidemia and insulin resistance. Rats will be fed with purify high-fat diet to induce obesity-insulin resistance. The effect of ALA、EPA、DHA on hyperlipemia and insulin sensitivity will be studied both on animal model and cell levels. Insulin sensitivity will be estimated by performing euglycemic hyperinsulinemic glucose clamp; fatty acids content in serum、live、adipose tissue and muscle will be analyzed; and gene expression of very low density lipoprotein synthesis(MTP、apoB-100)、cholesterol metabolism(HMG-CoA reductase、SREBP-2、ACAT)、high density lipoprotein metabolism(apoA-I、ABCA1、SR-B1) will be determined; what is more, the expression of IRS-1、GLUT4 in live、muscle、HepG2 and L6 cell will be assessed. Through this research, the mechanism of n-3PUFA on reducing serum lipid and improving insulin sensitivity will be gained.

N-3PUFA调节血脂代谢及胰岛素敏感性，而且类型与剂量影响调节效果，但机理尚不清楚，可能源自n-3PUFA对血脂代谢及胰岛素敏感性相关基因表达的调控。建立肥胖型胰岛素抵抗动物模型是研究血脂代谢异常、胰岛素抵抗的重要手段。本项目拟以纯合日粮诱发肥胖型胰岛素抵抗大鼠模型，从大鼠模型和细胞水平研究n-3PUFA对血脂代谢相关基因表达及胰岛素敏感性的调控。用高胰岛素-正常血糖钳夹技术评价胰岛素抵抗程度；气相色谱分析模型血清、肝脏、脂肪组织、肌肉中脂肪酸类型及含量；分析肝脏及HepG2细胞极低密度脂蛋白合成（MTP、apoB-100）、胆固醇代谢（HMG-CoA还原酶、SREBP-2、ACAT）、高密度脂蛋白胆固醇代谢（apoA-I、ABCA1、SR-B1）基因表达；检测肝脏、骨骼肌及HepG2细胞、L6细胞中IRS-1、GLUT4的表达。揭示n-3PUFA降低血脂及提高胰岛素敏感性的机制。