Biliary cholesterol secretion is closely coordinated with lecithin secretion and although both lipids are mobilized by bile salt from some intrahepatic site, the mechanizm of the transport of these lipids from the liver into bile has not been defined. Studies are designed to determint the mechanism by which particular lecithins (PC's) are mobilized from the liver into bile; to localize the intrahepatic site of orgin of biliary PC's; andto determine the extent to which specific PC's differing on their physical properties, influence serum cholesterol clearance, hepatic cholesterol uptake, and biliary cholesterol secretion. Proposed studies are based on our recent finding that the composition of biliary PC's can be radically changed and that this change is predicatd upon the formation of molecular species of PC which are highly hydrophilic. In initial studies, rats will be fed single fatty acids with different physical properties to determine 1. if changes in the compostion of PC's are accompanied by changes in serum and liver cholesterol concentrations and the secretion of cholesterol in bile; 2. the comparative rate of secretion from isolated perfused livers of individual PC's with different physical characteristics; and 3. the rate of solubilization by bile salt of different PC's from liver membranes. Studies next will be undertaken using lipoprotein-recombinants prepared with cholesterol and single species of PC that have different physical characteristis. Recombinants will be injected iv as a bolus to determine 1. the rate and extend of direct transfer of specific species of PC from the serum to liver to bile; 2. the extent of biliary PC secretion that occurs with PC remodelling (i.e., with deacylation and racylation of PC's in the liver); 3. by cell fractionation and a comparison of PC specific activities in hepatic fractions and bile, the pathway of transport of PC's into bile; and 4. the rate of serum cholesterol clearance and hepatobiliary cholesterol transport Since bile is the principal route for cholesterol elimination from the body, it may be possible to facilitate biliary cholesterol secretion and reduce body cholesterol stores by making available particular species of PC that are preferentially secreted in bile.
