Description

Steatosis is the process describing the retention of lipids within the cells due to the abnormal synthesis and breakdown of triglyceride fat. The liver is the major organ of lipid metabolism and is the main organ affected by steatosis. The risk factors associated with steatosis include diabetes metillus, obesity, hypertension, protein malnutrition and anoxia. Hepatic steatosis is also associated with chronic hepatitis C, caused by Hepatitis C Virus (HCV). Cytochrome b5 is a ubiquitous electron transport hemoprotein involved in a number of oxidative reactions. It is implicated in lipid biosynthesis, passing electron to several fatty acid desaturases. It also participates in the metabolism of xenobiotics and compounds of endogenous metabolism and plays an important role in P450 associated metabolism.

The inventors have developed a mouse model in which cytochrome b5 has been deleted in the liver (Hepatic cytochrome b5 Null (HBN) mouse). The loss of hepatic cytochrome b5 results in a reduction in metabolism and in the development of non-alcoholic hepatic steatosis (unpublished data). The mouse model presents an age related increase in hepatic lipid and this accumulation of hepatic microvesicular steatosis reached significance at 6 months. Additionally, while the overall hepatic and plasma lipid content is unchanged between the transgenic and the wild type mice, the fatty acid profiles are different, especially for the polyunsaturated fatty acids (n-6).

Application

The mouse model is a valuable in vivo tool to study the causes of non-alcoholic liver steatosis. The model would be useful for in vivo preclinical studies of new therapeutics to prevent or treat steatosis. Finally, the model may also be used to study the role of liver steatosis in metabolic diseases, such as diabetes mellitus, as well as in chronic hepatitis C disease.

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For more information please contact

Dr George Tzircotis

+44 (0) 20 3469 6300 .(JavaScript must be enabled to view this email address)