Establishment of rabbit model with nonalcoholic fatty liver disease induced by high-fat diet

Abstract

Objective To establish the rabbit model with nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) , and to investigate the course of the disease. Methods Forty-nine male healthy New Zealand white rabbits were divided into the control group (n=10) and the HFD group (n=32) by random digit method, and fed with standard diet and HFD, respectively. The HFD group was divided into the 4-week HFD group (HFD-4W, n=8) , 8-week HFD group (HFD-8W, n=8) , 12-week HFD group (HFD-12W, n=8) , and 16-week HFD group (HFD-16W, n=8) , and determined by blood biochemical test and liver pathological examination at each time point, respectively. Another 7 rabbits in the supplementary group were fed with HFD to be randomly included into the 4 HFD groups when the rabbits died. The general condition of the rabbits were observed, and the liver pathology of the rabbits was detected and evaluated by the NAFLD activity score (NAS). According to NAS, all the rabbits were divided into the normal group, nonalcoholic steatohepatitis (NASH) group and potential NASH group. The blood biochemical parameters of serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total bilirubin (TB) , triglyceride (TG) and total cholesterol (TC) were compared among groups. Results One rabbit died of unknown causes at 12 weeks in the control group. One rabbit died at 7 weeks in the HFD-8W group; One rabbit died at 8, 10, and 11 weeks in the HFD-12W group, respectively; Two rabbits died at 8 weeks and one rabbit died at 13 weeks in the HFD-16W group, respectively, and the cause of death was diarrhea. The thickened rabbit liver in the HFD group showed increased volume and faded color, and histopathological examination revealed hepatic steatosis, ballooning degeneration and lobular inflammation. The rabbits were divided into the normal group (n=9) , NASH group (n=19) and potential NASH group (n=13) according to the NAS, and there was no statistically significant difference in the serum ALT, AST and TB among the groups (all P>0.05). Compared with the normal group, the serum TG and TC levels increased in the potential NASH group and NASH group (all P 0.05). Conclusion The rabbit model with NAFLD induced by HFD is easily established, which can simulate the pathological and physiological characteristics of human NAFLD well. Key words: Nonalcoholic fatty liver disease; Models animal; High fat diet