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Mol Cell Biochem. 2005 Jan;268(1-2):53-8.

Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets may be a model of non-alcoholic steatohepatitis.

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  • 1Centre de Recerca Biomèdica, Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan, 43201-Reus, Catalunya, Spain.


The present study was aimed (1) to investigate the effect of cholesterol and fat enriched diets on the development of steatohepatitis in apolipoprotein E-knockout mice, and (2) to study the chronological relationships between the development of hepatic alterations, hypercholesterolemia and atherosclerotic lesions in this experimental model. The study consisted of two protocols. Protocol 1 was used in 90 mice subdivided in groups of 18. For 10 weeks, each group was given a diet with different fat and cholesterol contents. Protocol 2 was used in 42 mice, subdivided in four groups. Each group was given a diet enriched with cholesterol and palm oil and they were sacrificed at 8, 13, 18 and 24 weeks of age. Results were as following. (1) Mice given high fat/high cholesterol diets developed an impairment of liver histology consisting of fat accumulation, macrophage proliferation, and inflammation. (2) These effects were modulated by the type of fat: olive oil was mainly associated with macrovesicular steatosis and cholesterol plus palm oil with severe steatohepatitis. (3) There was a chronological and quantitative relationship between liver impairment and the formation of atheromatous lesions. We conclude that apolipoprotein E-knockout mice may be a useful model for investigating the mechanisms of diet-induced steatohepatitis.

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