HEPATIC TRANSPORT AND SECRETION OF UNESTERIFIED CHOLESTEROL IN THE RAT IS TRACED BY THE PLANT STEROL, SITOSTANOL

The hepatic uptake, transport, and secretion into bile of unesterified cholesterol cannot be directly quantitated because of extensive excha nge and equilibration between different pools of unesterified choleste rol. Plant sterols are structurally similar to cholesterol but because of poor intestinal absorption are ordinarily not present in the liver . To quantitate hepatic sterol uptake and transport in the absence of exchange with endogenous sterols, isolated rat livers were perfused wi th the plant sterol, sitostanol, incorporated in phosphatidylcholine l iposomes. Appreciable amounts of sitostanol were taken up by the liver and uptake was independent of the presence of bile salt. In contrast, like unesterified cholesterol, the secretion oi sitostanol in bile re quired bile salt. Sitostanol was detected in bile within 5 min after a perfusion was begun and reached a plateau by about 20 min. The rate o f appearance of sitostanol in bile was precisely the same as unesterif ied cholesterol when both sterols were perfused together. Furthermore, the output of sitostanol in bile was directly proportional to the out put of cholesterol. At the peak of biliary sitostanol secretion, the a mount of sitostanol relative to unesterified cholesterol was much grea ter in bile (40-50% of sterols) than in the whole liver (11% of sterol s). Selective biliary secretion of sitostanol was associated with much greater concentrations of sitostanol in canalicular membranes than in the interior membranes of the hepatocyte and in newly secreted high d ensity lipoproteins compared to newly secreted very low density lipopr oteins. These results indicate that sitostanol parallels the secretion from and distribution of unesterified cholesterol in the liver and su ggest that sitostanol can be used as a physiologic analog of unesterif ied cholesterol to trace the transport of sterols through the liver.