The contribution of newly synthesized cholesterol to biliary cholesterol in healthy humans

Hypersecretion of biliary cholesterol appears to be the key defect in the pathogenesis of cholesterol gallstones, and this may be due to an enhanced synthesis of cholesterol. To measure fractional syntheses of biliary and plasma cholesterol, five male and 3 female healthy humans with an intact enterohepatic circulation were infused intravenously with [1-13C]acetate for 15 h. Samples of duodenal bile and blood were taken hourly and an enteral formula diet was given. Free cholesterol mass distribution was analyzed by gas chromatography mass spectrometry. The Mass Isotopomer Distribution Analysis (MIDA) technique allowed to calculate fractional synthesis. After 6 hours of infusion, the [13C]label of the cytosolic acetate pool reached a plateau of approximately 12%. Individual fractional cholesterol synthesis is plasma and bile correlated significantly (6-15 h) and amounted to 4.2% and 5.3% after 15 h, respectively. It may be concluded from this study, that newly synthesized cholesterol is secreted into bile to a higher extent than into plasma.