Hepatic transport and secretion of unesterified cholesterol in the rat is traced by the plant sterol, sitostanol

• Published in: Journal of lipid research 1996-01, Vol.37 (1), p.15-21
• Main Authors: Robins, S.J. (Boston University of Medicine, Boston, MA.), Fasulo, J.M, Pritzker, C.R, Patton, G.M
• Format: Article
• Language: English
• Subjects: ACIDE BILIAIRE; ACIDOS BILIARES; Animals; Bile - metabolism; Bile Acids and Salts - metabolism; Cholesterol - analogs & derivatives; Cholesterol - metabolism; FITOSTEROLES; FOIE; HIGADO; In Vitro Techniques; Liver - metabolism; Male; Perfusion; PHYTOSTEROL; Radioactive Tracers; Rats; Rats, Sprague-Dawley; Sitosterols - metabolism
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)37631-8

The hepatic uptake, transport, and secretion into bile of unesterified cholesterol cannot be directly quantitated because of extensive exchange and equilibration between different pools of unesterified cholesterol. 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 with the plant sterol, sitostanol, incorporated in phosphatidylcholine liposomes. 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 of sitostanol in bile required 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 of appearance of sitostanol in bile was precisely the same as unesterified cholesterol when both sterols were perfused together. Furthermore, the output of sitostanol in bile was directly proportional to the output of cholesterol. At the peak of biliary sitostanol secretion, the amount of sitostanol relative to unesterified cholesterol was much greater in bile (40-50% of sterols) than in the whole liver (11% of sterols). 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 density lipoproteins compared to newly secreted very low density lipoproteins