FATZO-NAFLD/NASH Model

FATZO Mouse

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Dr Jean-Pierre Wery
CEO, Crown Bioscience Inc.

  • Develops NAFLD/NASH in an inherently dysmetabolic, obese, and diabetic mouse model. More closely resembles development of NAFLD/NASH in the context of dysmetabolism.
  • Polygenic model with an intact leptin pathway like humans
  • Elevated liver injury markers (ALT, AST) and liver trigycerides on a “western” diet
  • Consistently develops various pathologies associated with NAFLD/NASH: steatosis, hepatocyte ballooning, inflammation, and fibrosis
  • Available for NAFLD/NASH studies at CrownBio site or for internal evaluation at your site.

Model Description:

The FATZO-NAFLD/NASH model was created by inducing NAFLD/NASH by administration of a “western diet.” On diet, the model develops steatosis, hepatocyte ballooning, inflammation, and fibrosis over time.

Western Diet: 21% fat, 0.2% cholesterol, 5% fructose in drinking water.



FATZO Mouse Background:

The FATZO mouse is an inbred polygenic animal model for obesity, metabolic syndrome, and diabetes. The FATZO mouse was created by crossing of the AKR/J and C57BL/6J strains followed by selective inbreeding. These two strains are very sensitive to developing obesity and metabolic syndrome under the influence of high fat diets. Both strains develop leptin resistance while gaining adiposity. However, under the same feeding conditions, AKR/J mice gain more weight, have higher carcass lipid content, plasma leptin, insulin and triglyceride concentrations, and are more insulin resistant, but are less hyperglycemic and less glucose intolerant than C57BL/6J mice. The crossing of these two strains and the selective inbreeding of the subsequent generations has resulted in a strain exhibiting obesity in a pre-diabetic state which slowly progresses to overt diabetes.

Phenotype:

  • Elevated body weight, body fat, and liver weight on a western diet
  • Elevated serum markers of liver injury (ALT, AST) and elevated liver triglycerides
  • Develop steatosis by 4-8 weeks on a western diet
  • Hepatocyte ballooning and inflammation observed by 16 weeks on western diet
  • By 20 weeks on western diet, the FATZO mouse develops NASH and shows fibrosis
  • FATZO model develops NAFLD/NASH in an inherent mouse model of type 2 diabetes when fed a western diet + fructose

FATZO-NAFLD/NASH Model Develops NAFLD Progressing into NASH
by 20 Weeks on a Western Diet

Figure 1: Scoring for progression of NAFLD/NASH pathologies in individual mice. Each dot represents an individual mouse in a cohort, either on a standard diet (blue) or on western diet (orange).

Development of Fibrosis by 20 weeks in FATZO-NAFLD/NASH Model (Picosirius Red Staining)

Figure 2: Progression of fibrosis in FATZO-NAFLD/NASH model (Picosirius red staining). Arrows mark fibrotic processes.

FATZO-NAFLD/NASH Model Health Report:

HEALTH REPORT

Publicatons:

The FATZO Mouse Fed a Western Diet + 5% Fructose Develops NAFLD and NASH