, Volume 343, Issue 1-2, pp 59-66
Date: 29 May 2010

Differential response of two models of genetically modified mice fed with high fat and cholesterol diets: relationship to the study of non-alcoholic steatohepatitis

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Research on the molecular basis of the hepatic alterations associated to obesity is dependent on the availability of suitable animal models. Apolipoprotein E deficient mice (ApoE−/−) and LDL-receptor deficient mice (LDLr−/−) develop steatosis and steatohepatitis when given pro-atherogenic diets. However, previous data suggest that these two models are not completely interchangeable, and that their metabolic phenotype may partially differ in response to nutrient stimuli. The present study further investigates this question, by comparing changes in hepatic inflammation, lipoprotein metabolism, and their related gene expressions. LDLr−/− mice were more susceptible to the development of obesity and hepatic steatosis, while the ApoE−/− model increased the amount of macrophages and inflammatory nodules in the liver. These changes were accompanied by a differential expression of selected members of the MAPK family and PPARs in the liver.

F. Rodríguez-Sanabria and A. Rull contributed equally to this work.