The db mouse as a model for steatohepatitis

Includes bibliographical references.Fatty liver disease is a collective phrase for a spectrum of diseases characterised by increased liver fat content. It ranges from fatty infiltration of the liver to an inflammatory condition, steatohepatitis, which may lead onto cirrhosis. Although not associated with alcohol consumption, non-alcoholic steatohepatitis (NASH) has strong associations with obesity, diabetes and dyslipidaemia. Overlapping pathological mechanisms may be involved. The course of the disease will remain unpredictable, and specific treatment will only be able to be instituted once the pathogenesis is fully understood. This thesis reviews current understanding of the pathogenesis and explores the suitability of a recently defined obese diabetic mouse model for its value as a model in the heterozygous and homozygous states. Observations revealed that the db/wt phenotype has a larger mass than the wt/wt and responds with hyperglycaemia. Lipid accumulation occurs in this model when alcohol is administered and lipid peroxidation occurs but histological changes of steatosis and steatohepatitis do not occur. The db/db model is phenotypically distinguished by a large amount of fat storage, diabetes and macrovesicular steatosis that has more lipid peroxidation but no steatohepatitis even when alcohol further increases lipid peroxidation. The model, as explored, did not reveal steatohepatitis either alone, or with alcohol as a single additional stressor, but both the db/wt and db/db mouse model could be further investigated to explore whether additional stressors could induce steaotohepatitis in this model