S1845 Combining Genetic and Dietary Factors in Creation of a Novel Model of Nonalcoholic Steatohepatitis (NASH) in Mice

Abstract

Aim: To characterize hepatocyte apoptosis in a nutritional model of steatohepatitis induced by modified atherogenic diet (M-Ath). Methods: Liver tissue samples were obtained at sacrifice from 5 animals belonging to 4 treatment groups (control, fructose, atherogenic, and M-Ath). Hepatocyte apoptosis in liver sections was quantified by counting the number of TUNEL positive cells in 10 random microscopic fields (x 40). Caspase 3 activity was measured in liver tissue lysate following 19 hr incubation. Results: Compared to controls, the number of TUNEL positive hepatocytes was not different in atherogenic and M-Ath diet groups, but the fructose group had significantly lower number of TUNEL positive hepatocytes. Pigs in the M-Ath diet had significantly higher Caspase 3 activity when compared to the other three groups. There was no detectable Caspase 3 activity in liver lysate of the fructose group pigs. Serum ALT values were not different among control, atherogenic and M-Ath diets but the fructose group had significantly lower ALT values. Conclusions: Feeding Ossabaw pigs a modified atherogenic diet resulted in the development of abnormal liver histology associated with increased caspase 3 activity as a marker of hepatocyte apoptosis. These results identify a relevant experimental model for studies to understand the pathophysiology of NASH development as well as to test novel treatment strategies for patients with this condition.