Apolipoprotein E regulates dietary cholesterol absorption and biliary cholesterol excretion: Studies in C57BL/6 apolipoprotein E knockout mice

The present study examined the role of apolipoprotein E (apoE) in the regul ation of dietary cholesterol absorption and biliary cholesterol excretion. increasing dietary cholesterol from 0.02% to 0.5% in C57BL/6 wild-type mice decreased the percentage of dietary cholesterol that is absorbed by 25%, a nd this decrease was associated with a 2-fold increase in gallbladder bilia ry cholesterol concentration. In contrast increasing dietary cholesterol fr om 0.02% to 0.5% in C57BL/6 apoE knockout mice produced no significant supp ression of the percentage dietary cholesterol absorption and increased gall bladder biliary cholesterol concentration only 16%. Whereas in wild-type mi ce. the increase in dietary cholesterol increased the hepatic excretion of biliary cholesterol 4-fold, there was only a 2-fold increase in apoE knocko ut mice. On both the low- and the high-cholesterol diets, whole liver and i solated hepatocyte cholesterol content was higher in the apoE knockout mice . These results suggest that, in response to dietary cholesterol, apoE may play a critical role in decreasing the percentage absorption of dietary cho lesterol and increasing biliary cholesterol excretion. These observations s uggest a mechanism whereby the absence of apoE contributes to the propensit y for tissue cholesterol deposition and accelerated atherogenesis in apoE k nockout mice.