E. Sehayek et al., BILIARY CHOLESTEROL EXCRETION - A NOVEL MECHANISM THAT REGULATES DIETARY-CHOLESTEROL ABSORPTION, Proceedings of the National Academy of Sciences of the United Statesof America, 95(17), 1998, pp. 10194-10199
The regulation of dietary cholesterol absorption,vas examined in C57BL
/6 and transgenic mice with liver overexpression of the scavenger rece
ptor BI (SR-BI Tg), In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) die
tary cholesterol resulted in a dose-dependent decrease in the percenta
ge of dietary cholesterol absorbed. A plot of total daily mass of diet
ary cholesterol absorbed versus the percentage by weight of cholestero
l in the diet yielded a curve suggesting a saturable process with a K-
m of 0.4% (wt/wt) and a V-max of 0.65 mg cholesterol/g body weight per
day. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutary
l CoA reductase activity, stimulated cholesterol 7 alpha-hydroxylase a
ctivity, and enhanced fecal excretion of bile acids, but none of these
changes correlated with the percentage of dietary cholesterol absorpt
ion. Dietary cholesterol also caused an increase in biliary cholestero
l concentration, and in this case the concentration of biliary cholest
erol was strongly and inversely correlated with the percentage dietary
cholesterol absorption (r = -0.63, P < 0.0001). Biliary cholesterol c
oncentration was also directly correlated with daily cholesterol intak
e, dietary cholesterol mass absorption, and liver cholesterol ester co
ntent. Transgene-induced overexpression of SR-BI resulted in a stimula
tion of excretion of cholesterol into the bile and suppressed percenta
ge dietary cholesterol absorption. Furthermore, biliary cholesterol le
vels in SR-BI Tg mice were strongly and inversely correlated with the
percentage of dietary cholesterol absorbed (r = -0.99, P < 0.0008). In
summary, these results suggest that the excretion of cholesterol into
the bile plays an important role in regulating the percentage absorpt
ion of dietary cholesterol.