Carbon Tetrachloride (CCl4) is a common hepatotoxin used in liver injury and fibrosis animal models, but it is rare to observe obesity and liver fat accumulation in CCl4-induced liver fibrosis models since weight loss is also provoked. Nonalcoholic Steatohepatitis (NASH) is an epidemic disease coincides with obesity and type 2 diabetes (T2D) causing liver steatosis and inflammation. There are no perfect animal models that capture all steatosis, inflammation and following fibrosis stages of NASH disease, our recent study developed an accelerated fibrotic model in previously established NASH model of western diet fed FATZO/pco mice. Using a dose of 0.08 mL/kg (IP, 2/week) CCl4 on 8-week western diet fed FATZO/pco mice, the average histology fibrosis score increased from 1.2±0.2 to 3.0±0.0, average lobular inflammation score increased from 1.4±0.7 to 1.9±0.1, while average steatosis score remained stable. Hepatotoxicity of CCl4 affected the hepatocyte ballooning score due to increased necrosis, reducing ballooning score from 1.6±0.4 to 1.0±0.0. It is also interesting to find out the FATZO/pco strain tolerated CCl4 challenges better than the control C57Bl/6 strain.
Conclusion: The study developed an accelerated NASH mice model with balanced performance in all stages of histopathology and provides better translational values in comparison with human patients.
G. Zhang: None. K. Chng: None. Y. Wang: None.