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.

1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.–m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01–11.90) versus 18.60 (3.20–32.60) μg/100 μg of protein, P <0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity ( L s / S ) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean ± sem , 37.6 ± 1.3 versus 33.8 ± 0.6, P <0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically( L S / S correlated negatively with glycophorin sialic acid content, r = 0.73, P <0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes.