Experimental non-alcoholic fatty liver disease causes regional liver functional deficits as measured by the capacity for galactose metabolism while whole liver function is preserved

Abstract

Abstract Background Increasing incidence of non-alcoholic fatty liver disease (NAFLD) calls for improved understanding of how the disease affects metabolic liver function. Aims To investigate in vivo effects of different NAFLD stages on metabolic liver function, quantified as regional and total capacity for galactose metabolism in a NAFLD model. Methods Male Sprague Dawley rats were fed a high-fat, high-cholesterol diet for 1 or 12 weeks, modelling early or late NAFLD, respectively. Each NAFLD group (n = 8 each) had a control group on standard chow (n = 8 each). Metabolic liver function was assessed by 2-[18F]fluoro‐2‐deoxy‐D-galactose positron emission tomography; regional galactose metabolism was assessed as standardised uptake value (SUV). Liver tissue was harvested for histology and fat quantification. Results Early NAFLD had median 18% fat by liver volume. Late NAFLD had median 32% fat and varying features of non-alcoholic steatohepatitis (NASH). Median SUV reflecting regional galactose metabolism was reduced in early NAFLD (9.8) and more so in late NAFLD (7.4; p = 0.02), both significantly lower than in controls (12.5). In early NAFLD, lower SUV was quantitatively explained by fat infiltration. In late NAFLD, the SUV decrease was beyond that attributable to fat; probably related to structural NASH features. Total capacity for galactose elimination was intact in both groups, which in late NAFLD was attained by increased fat-free liver mass to 21 g, versus 15 g in early NAFLD and controls (both p ≤ 0.002). Conclusion Regional metabolic liver function was compromised in NAFLD by fat infiltration and structural changes. Still, whole liver metabolic function was preserved in late NAFLD by a marked increase in the fat-free liver mass.