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:
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.
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.
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
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.
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