RenaSci has established and validated a genetically obese NASH and fibrosis rodent model, the ob/ob H-FFC mouse. In this model ob/ob mice are maintained on a high-fat, high-fructose, high-cholesterol diet for 12 weeks. These mice are obese and develop many of the features of steatohepatitis and fibrosis observed in man. Specifically, they have increased:

• Plasma ALT and AST
• Liver lipids and collagen content
• Histological end points: lipid deposition, lobular inflammation, overall NAS score and moderate to marked fibrosis

The ob/ob H-FFC mouse has been validated with the peroxisome proliferator activated receptor (PPAR) gamma agonist, pioglitazone, and the dual PPAR alpha/delta agonist, elafibranor.

 

Effects of pioglitazone & elafibranor
on liver pathology in ob/ob mice

 

Mean and SEM (n=11-13). Significances vs ob/ob standard chow vehicle are denoted by *p<0.05, **p<0.01 and ***p<0.001. Significances vs ob/ob H-FFC vehicle are denoted by ††p<0.01 and †††p<0.001.
* The NAFLD activity score (NAS) generated by combining scores for # parameters; steatosis, hepatocellular ballooning and lobular inflammation.

 

 

Sirius red stained liver

Representative images from the NASH and fibrosis rodent model. Sirius red stained liver sections, magnification 10x demonstrating the
difference between the ob/ob vehicle, ob/ob H-FFC vehicle, Pioglitazone 15 mg/kg po bid and Elafibranor 30 mg/kg po qd groups

 

The ob/ob H-FFC mouse is obese

Data are presented as means and % represent differences from standard chow group on the final day of the study. A: there were no significant differences between the ob/ob standard chow and ob/ob H-FFC vehicle group body weights. Elafibranor significantly (p<0.05) reduced body weight from ob/ob standard chow on Days 7-85 and from the ob/ob H-FFC vehicle group on Days 5-85. B: the body weight of the ob/ob H-FFC vehicle group was significantly (p<0.05) higher than the ob/ob standard chow group on Days 6-11 and lower on Days 61-85. Pioglitazone significantly (p<0.05) increased body weight from ob/ob standard chow and ob/ob H-FFC vehicle on Days 2-85.

 

 

Get in touch to learn more about RenaSci’s ob/ob H-FFC mouse model of NASH and fibrosis.

 

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