title: Phenotyping murine models of non-alcoholic fatty liver disease through metabolic profiling of intact liver tissue.
abstract: NAFLD (non-alcoholic fatty liver disease) 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. The present study aimed to characterize 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 (1)H MAS (proton magic angle spinning) MRS (magnetic resonance spectroscopy), showed an increase in the 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 six out of eight 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 (1)H MAS MRS studies may inform subsequent in vivo MRS studies at lower field strengths.
authors.affiliation: Department of Hepatology and Gastroenterology, Imperial College London, St Mary's Hospital Campus, London, U.K. j.cobbold@imperial.ac.uk
authors.forename: Jeremy F L
authors.initials: JF
authors.lastname: Cobbold
authors.forename: Quentin M
authors.initials: QM
authors.lastname: Anstee
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldin
authors.forename: Horace R T
authors.initials: HR
authors.lastname: Williams
authors.forename: Helen C
authors.initials: HC
authors.lastname: Matthews
authors.forename: Bernard V
authors.initials: BV
authors.lastname: North
authors.forename: Nathan
authors.initials: N
authors.lastname: Absalom
authors.forename: Howard C
authors.initials: HC
authors.lastname: Thomas
authors.forename: Mark R
authors.initials: MR
authors.lastname: Thursz
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cox
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
authors.forename: I Jane
authors.initials: IJ
authors.lastname: Cox
mesh_terms: D000818:Animals; D001699:Biometry / Q000379:methods; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D055442:Metabolome; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009765:Obesity / Q000378:metabolism; D010641:Phenotype; D013045:Species Specificity
chemical_list: D004041:Dietary Fats; D008055:Lipids