Vitamin A metabolism in rat liver: a kinetic model

Vitamin A metabolism in the liver involves both hepatocytes and the nonparenchymal perisinusoidal stellate cells. To describe and quantitate the dynamic relationships between retinol in these cells and in plasma, we administered either chylomicrons labeled with [3H]retinyl esters or plasma containing [3H]retinol-retinol-binding protein-transthyretin to rats. Radioactivity and retinol masses were measured in plasma, liver, and isolated hepatocytes for 15 days; data were analyzed by model-based compartmental analysis. The resulting model predicts that: 1) approximately 20% of the total plasma turnover of retinol goes to the liver (vs. nonhepatic tissues) and approximately 20% of plasma retinol input is from liver (vs. nonhepatic tissues), 2) about one-half of the retinol recycling from plasma to liver is taken up by hepatocytes and about one-half by nonparenchymal cells, 3) retinyl esters in both cell types are derived preferentially from newly taken up retinol rather than from the main intracellular retinol pools, and 4) at least one-half of the retinol secreted by hepatocytes of rats consuming low levels of vitamin A is directly transferred to nonparenchymal cells. In addition, the data are compatible with the hypothesis that retinol-binding protein is the vehicle for transfer of retinol from hepatocytes to nonparenchymal stellate cells and between plasma and liver cells.