【Animal Modeling】-Fatty Liver Compound Model

       [Modeling method] ApoE- can create ob/ob mice + MCD diet, db/db mice + MCD diet, Abcb11 mice + MCD diet and other animal models by combining genetic modification and nutritional factors according to the rules of human NAFLD . /-Mouse + HFD, PPARa-/-mouse + MCD diet, etc.

  [Model Features] All complex models can cause insulin resistance, obesity, steatohepatitis and fibrosis. Among them, the db/db mouse + MCD diet model is more serious than the ob/ob mouse + MCD diet model. Inflammation, peripheral fibrosis are more serious, obesity, hyperinsulinemia and hyperleptinemia are significantly shorter. After induction with the MCD diet, PPARa-/- mice showed significantly more NAFLD performance than the control group.

  [Assessment and application of models] The pathological changes and etiology of existing animal models vary due to modeling methods, and there is no model that can fully express the pathological changes and pathophysiological processes of human FLD. Genetic changes in transgenic models can lead to impaired fat metabolism and oxidative stress, but human NAFLD is mainly related to genetic susceptibility and insulin resistance. Transgenes tend to produce HAC and HCC. The causes of fatty liver caused by excessive dietary intake are not yet known. Therefore, the food components most likely to cause obesity and fatty liver and all genetic and environmental factors that regulate human energy metabolism are also unknown. It is difficult to control these factors. Therefore, controlling food composition and food intake in animal models is a better way to study fatty liver diets related to obesity. However, diet-induced obesity and fatty liver have certain differences between rodents of different breeds, ages, and sexes. For example, the severity and progress of the MCD model depends on sex, strain, and type of experimental animals. This composite model maximizes the complexity of human NAFLD, with great pathological changes and great potential.

  Researchers should select appropriate animal models based on research goals, technical level and laboratory conditions. The selected animal model should be consistent with the research goal, and the model has a high replication rate, such as ob/ob and db/higher than db mice, which are commonly used in laboratory research of metabolic related diseases. Wide and easy to use. It is also necessary to continuously improve the modeling method by improving the pure animal feeding and nutrition formula and the timely use of new technologies, new methods and new indicators in animal experiments.