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

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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.

Original languageEnglish
Article number541
JournalBMC Gastroenterology
Number of pages10
Publication statusPublished - 2022

    Research areas

  • Animals, Rats, Male, Non-alcoholic Fatty Liver Disease/pathology, Galactose/metabolism, Rats, Sprague-Dawley, Liver/pathology, Diet, High-Fat/adverse effects

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