Quantitative studies on fatty acid metabolism in isolated parenchymal cells from normal and cirrhotic livers in rats

Parenchymal cells isolated from normal and thioacetamide-induced micronodular cirrhotic rat livers were used to evaluate changes in hepatocellular fatty acid (FA) metabolism in cirrhosis. Exogenous free FA (FFA) are rapidly taken up by hepatocytes obtained either from normal or cirrhotic livers. They are predominantly esterified to triglycerides and accumulate intracytoplasmatically as lipid droplets with increasing cellular FFA uptake. In the parenchymal cells of cirrhotic livers, however, the following changes were observed when compared with controls: (i) decreased cellular output of esterified FA derived both from exogenous sources and from de novo FA synthesis; (ii) increased total ketone body production, mainly as beta-hydroxybutyrate; (iii) decreased cholesterol synthesis; and (iv) enhanced incorporation of newly synthesized FA into phospholipids in spite of an unaffected rate of FA synthesis. In summary, the data provide evidence for intrinsic alterations in the lipid metabolism in the parenchymal cells of cirrhotic livers which are preserved in the isolated hepatocytes under optimum incubation conditions for oxygen and substrate supply.