BILIARY CHOLESTEROL EXCRETION - A NOVEL MECHANISM THAT REGULATES DIETARY-CHOLESTEROL ABSORPTION

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.