Journal of Lipid Research, Vol 37, 15-21, Copyright © 1996 by Lipid Research, Inc.
Hepatic transport and secretion of unesterified cholesterol in the rat is traced by the plant sterol, sitostanol
SJ Robins, JM Fasulo, CR Pritzker and GM Patton
Veterans Administration Medical Center, Boston University School of Medicine, MA 02130, USA.
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. These results indicate that sitostanol parallels
the secretion from and distribution of unesterified cholesterol in the
liver and suggest that sitostanol can be used as a physiologic analog of
unesterified cholesterol to trace the transport of sterols through the
liver.
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