The contribution of newly synthesized cholesterol to biliary cholesterol in the rat

The current studies were undertaken to quantitate the proportion of biliary cholesterol that is newly synthesized in the rat and to determine whether this proportion is influenced by the rate of hepatic cholesterol synthesis. Female rats were subjected to total biliary diversion either immediately preceding, or 6 hr following, the intravenous administration of [³H]water. When diversion was commenced just before administration of the [³H]water, the amount of newly synthesized sterol secreted in the bile in relation to the total cholesterol secretion rate increased during the first few hours of diversion but by the 7th and 8th hours the proportion had become essentially constant at about 18%. When a continuous infusion of bile acid was given, the output of both total and labeled cholesterol increased several-fold, but the proportion of the total that was newly synthesized was unchanged. Under conditions where biliary diversion was not commenced until 6 hr following the administration of the [³H]water, newly synthesized sterol again contributed only 16% of the total biliary cholesterol. When that rate of hepatic cholesterol synthesis was increased 2.5-fold by feeding cholestyramine, 34% of total biliary cholesterol was newly synthesized, whereas when synthesis was suppressed by feeding cholesterol or by fasting for 48 hr this porportion decreased to 3.5% and 1.7%, respectively. However, there was no significant change in total biliary cholesterol output under these conditions. In other experiments it was shown that the specific activity of the unesterified cholesterol in bile was significantly higher than that of any other tissue, including the liver, plasma, and several extrahepatic tissues.