The Roles Of The Key Genes Of Lipid Metabolism In Non-alcoholic Fatty Liver Disease In High Fat Diet LDLR^-/- Mice

Non-alcoholic fatty liver disease (NAFLD) is the pathological syndrome with the diffuse liver steatosis bullous as the main feature, clear exception of alcohol and other factors that damage the liver. NAFLD includes a series of interrelated pathological changes, including simple hepatic adipose infiltration and nonalcoholicsteato-hepatitis (NASH) and fatty hepatic cirrhosis. NAFLD is a relatively common liver complication of type 2 diabetes mellitu (T2DM)s, insulin resistance (IR) ,and central obesity. Statistics shows that 2.6% of normal weight children, 52.8% of obese children have NAFL, and NASH incidence in the population has reached 2% -3%. Recent studies suggest that simple hepatic adipose infiltration have a good prognosis, while almost half the NASH patients may be developed to liver fibrosis, about 15% progress to cirrhosis, 3% deteriorate to liver failure. However, the molecular mechanism of NAFLD have not yet completely clear.In the present thesis some researches on the potential role of the lipid metabolism in promoting the mouse steatosis have been carried out.We have established an NAFLD mouse model by a high fat diet (HFD) on low density lipoprotein receptor deficient mice. In the experiment 3 weeks of age mice were fed HFD and standard diet (ND), and dissected in 3,6,10,14 and 18 weeks of age derived. Then, hepatic lipid metabolism gene expression differences between HFD and ND mice were detected by real time quantitative RT-PCR. At the same time the blood biochemical parameters and liver morphology were detected. The results are as follows:1.The blood biochemical parameters:Compared with ND mice, the HFD group mice showed weight gain, insulin levels and IR increased when 6 weeks of age and continued to 18 weeks of age. Moreover, blood glucose of HFD fed mice at 18 weeks of age increased significantly. The HFD group mice at 6 weeks of age showed substantial increases in plamsma total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (LDL-C), and continued to 18 weeks of age. Meanwhile, alanine amino transferase(ALT) and aspartate aminotransferase (AST) were significantly higher (P <0.01) respectively from 10 weeks and 14 weeks of age ,continued to 18 weeks of age. T2DM mice From 6 weeks of age, liver FFA content compared with ND mice were significantly increased and continued to 18 weeks of age.2.Detection of liver morphology:the HFD group mice at 6 and10 weeks of age lipid droplets within the liver cytoplasm were observed by Oil red O staining, showing hepatic steatosis, and increasing the degree of hepatic steatosis at 14 and 18 weeks of age. ND mice of all ages showed liver tissue integrity, clear hepatic lobules and lipid deposition were not observed in significant.3. Gene expression differences: Compared with the ND group mice, HFD group mice showed that the following changes in gene expression, liver X receptorα( LXRα), SREBP1c, glycogen synthase kinase (GSK3β) and acetyl CoA carboxylaseα(ACCα), fatty acid synthase (FAS) and Stearoyl-CoA desaturase-1(SCD1), acetyl CoA carboxylaseβ(ACCβ) and glycerol phosphate acyltransferase(GPAT) expression was significantly higher (P <0.05).It play an important role during the formation and development of mice adiposis hepatica that metabolism factor LXRαand SREBP1c through the promotion of liver fatty acid synthesis.