Aims: Animal models of NAFLD give crucial information, not only pathogenesis of NAFLD but also therapeutic effects of various agents. We investigated the degree of steatosis, inflammation and fibrosis of the liver obtained from three animal models of ...
Aims: Animal models of NAFLD give crucial information, not only pathogenesis of NAFLD but also therapeutic effects of various agents. We investigated the degree of steatosis, inflammation and fibrosis of the liver obtained from three animal models of NAFLD with different mouse species and diets.
Methods: Group1: The mice were fed a control diet. Group2: The gene responsible for the production of leptin deficient ob/ob mice fed a 60% fat diet. Group3: The leptin receptor deficient db/db mice were fed a diet deficient in methionine and choline (MCD) diet. Group4: The leptin receptor deficient db/db mice were fed a 60% fat + 2.5% cholesterol diet and drinking water (55% fructose, 45% glucose w/w). Change of body weight was observed and blood was collected before sacrifice. After being sacrificed, the liver tissues were collected and fixed in formalin. Histological evaluation was conducted by blindly pathologist.
Results: The body weight in group1 & 2 & 4 (control & high-fat-diet fed mice) were increased during the study, whereas group3 (MCD feeding mice) showed weight loss for unclear reasons. Liver histology showed no significant difference in hepatic steatosis and inflammation among the three groups (group2-4). Meanwhile, liver fibrosis was slightly more frequent in group3 than that in groups2 and 4. However, the maximum degree of fibrosis in group3 was Ib. The level of liver enzyme showed no significant difference, whereas the level of triglyceride was significantly increased in group4 (TG: 30.8±3.2 (group1), 31.8±4.9 (group2), 32.8±1.7 (group3), 141±15.20 (group4) (p < 0.001) (mg/dL)).
Conclusions: The results show that the three animal models are thought to induce hepatic steatosis and inflammation very well, but the induction of hepatic fibrosis is still considered to be limited. A better animal model development or integration model would be needed.