Phenotyping murine models of non-alcoholic fatty liver disease through metabolic profiling of intact liver tissue.
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.
Cobbold
Jeremy F L
JF
Department of Hepatology and Gastroenterology, Imperial College London, St Mary's Hospital Campus, London, U.K. j.cobbold@imperial.ac.uk
Anstee
Quentin M
QM
Goldin
Robert D
RD
Williams
Horace R T
HR
Matthews
Helen C
HC
North
Bernard V
BV
Absalom
Nathan
N
Thomas
Howard C
HC
Thursz
Mark R
MR
Cox
Roger D
RD
Taylor-Robinson
Simon D
SD
Cox
I Jane
IJ
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
D004041:Dietary Fats; D008055:Lipids