Experimental Study On Early Non - Alcoholic Fatty Liver Disease In Mice

Nonalcoholic fatty liver disease (NAFLD) is a progressive disease that includes simple steatosis (nonalcoholic fatty liver, NAFL), steatohepatitis (nonalcoholic steatohepatitis, NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Rehabilitation may happen when appropriate treatment is given at the stage of NAFL and NASH. This paper aims to establish a mouse model which is analogous to the progress of clinical nonalcoholic steatohepatitis and to explorate an experimental technology which can be used for noninvasive diagnosis of liver fat accumulation.Three parts were discussed here:1. The glucolipid metabolic profiles of 3 kinds of obesity and fatty liver mouse models, which were induced by high-fat high-calorie diet, were investigated. Meanwhile, the effects of fenofibrate were observed.2. A NASH mouse model, which was analogous to the characters of clinnical nonalcoholic steatohepatitis, was established by the high-fat diet combined with methionine choline-deficient diet.3. A semi-quantitative method with ultrasound echo-intensity attenuation coefficient was established for the evaluation of liver lipid accumulation in mice.The results showed that,1. The NIR and IR mice, which were induced by high-calorie diet, and the KKAy mice, which are spontaneous type 2 diabetes, were NAFL models. Accompanying with insulin resistance and obesity, hypercholesterolemia presented in NIR and IR mice, while complex hyperlipidemia presented in KKAy mice. The effects of fenofibrate on reducing liver lipid accumulation, losing weight and regulating blood lipid disorders in both NIR and IR models, and the contra effects in KKAy mice, were observed, respectively. However, the improving effect of fenofibrate on insulin resistance was showed similarly in all of the three models.2. The mice administrated with a high-fat diet combined with MCD4 diet showed the characters of NASH, such as liver lipid accumulation, elevated serum transaminase, obesity, hypercholesterolemia, and so on.3. The values of echo-intensity attenuation coefficient were positively associated with the content of hepatic triglyceride (r= 0.744) in mice. This method could be used to evaluate the pathological changes of hepatic lipid accumulation in mice.In conclusion, the characters of NAFL were observed in the high-diet-induced NIR and IR mice and KKAy mice, respectively. The responses to fenofibrate were quite different among these three mouse models. On the basis of NAFL model, a NASH model accompanied with some characters of metabolic syndrome was established with the MCD4 fourmula. In addition, the accumulation of fat in liver of mice can be measured by echo-intensity attenuation coefficient method.