RenaSci’s H-FFC mouse develops a robust NASH and fibrosis phenotype within a 12 week period.  Utilizing a high-fat, high-fructose, high-cholesterol (H-FFC) diet the overweight H-FFC mouse has advantages over the traditional MCD and CD dietary models, both of which induce weight loss. The RenaSci H-FFC mouse model is therefore more akin to the clinical presentation of the disease.

 

The mice in the model are maintained on a H-FFC diet for 12 weeks, this results in an increase in the following parameters:

• Plasma levels of liver enzymes (ALT and AST)
• Liver lipids
• Histological endpoints of NASH (for example; steatosis, hepatocellular ballooning and lobular inflammation) overall NAS and  fibrosis scores

 

The dual PPAR alpha /delta agonist, elafibranor reduces or inhibits many of the features of NASH and fibrosis in RenaSci’s H-FFC mouse. This demonstrates its usefulness as a model to identify potential treatments of NASH and fibrosis.

 

 

 

The H-FFC mouse, a robust model of NASH and fibrosis

 

The data is shown as adjusted means (n =11-12) and standard errors of the mean (SEM). The significance vs standard chow control denoted by ***p <0.001.
The significance vs H-FFC diet control denoted by †p <0.05, ††p <0.01 and †††p <0.001. * The NAFLD activity score (NAS) are generated by combining scores for # parameters.

 

 

The data is shown as adjusted means (n =11-12) and standard errors of the mean (SEM) are calculated from the residuals of the statistical models. Analysis was by robust regression (AST, ALP) and general linear model (ALT) of log transformed data with treatment  as a factor and termination order and day 1 body weight as covariates. The comparisons to the standard diet Group A were by the multiple t-test and significances are denoted by ***p <0.001. The comparisons of treatments to H-FFC diet group B were by the multiple t-test and significances are denoted by ††p <0.01 and †††p <0.001.

 

 

 

 

Sirius red stained liver

 

 

    

 

 

The H-FFC mouse is overweight

 

 

RenaSci’s H-FFC mouse had significantly (p <0.05) increased body weight compared to the standard chow vehicle from Day 2, except for on Days 6-14 and 17. Elafibranor significantly (p <0.001) reduced body weight versus standard chow vehicles from Day 3 and versus the H-FFC vehicle group from Day 2. Elafibranor decreased body weight by 20% compared to the standard diet vehicles and 29% compared to the H-FFC vehicle controls.

 

 

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