Phenotyping murine models of non-alcoholic fatty liver disease through metabolic profiling of intact liver tissue
Résumé
Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, associated with the metabolic syndrome. Effective techniques are needed to investigate the potential of animal models of NAFLD. This study aimed to characterise murine models of NAFLD by metabolic profiling of intact liver tissue. Mice of three strains (BALB/c, C3H and the novel mutant, Gena/263) were fed a control or high fat diet. Biometric, biochemical and histological analysis demonstrated a spectrum of NAFLD from normal liver to steatohepatitis. Metabolic profiling of intact liver tissue, using magic angle spinning proton magnetic resonance spectroscopy (MAS MRS), showed an increase in total lipid-to-water ratio, a decrease in polyunsaturation indices and a decrease in total choline with increasing disease severity. Principal components analysis and partial least squares discriminant analysis showed separation of each model from its control and of each model from the total dataset. Class membership from the whole dataset was predicted with 100% accuracy in 6 of 8 models. Those models with steatosis discriminated from those with steatohepatitis with 100% accuracy. The separation of histologically-defined steatohepatitis from simple steatosis is clinically important. Indices derived from 1H MAS MRS studies may inform subsequent in vivo MRS studies at lower field strengths.
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