Dietary cholesterol is secreted in intestinally derived chylomicrons during several subsequent postprandial phases in healthy humans

Background: The process of intestinal absorption and chylomicron resecretio n of dietary cholesterol in humans is poorly understood. Objective: The present study aimed to test the hypothesis that dietary chol esterol ingested during a given meal is resecreted into chylomicrons (and p lasma) during several subsequent postprandial periods. Design: Seven healthy subjects ingested 3 comparable mixed test meals (at 0 , 8, and 24 h) containing a given amount of fat (49 g) and cholesterol (157 mg); blood samples were taken 3 and 6 h after each test meal and 48 and 72 h after the beginning of the experiment. Heptadeuterated dietary cholester ol was present in the first test meal only, enabling its specific determina tion with use of gas chromatography-mass spectrometry. Chylomicrons, LDL, a nd HDL were isolated and lipids were quantified. Results: In apolipoprotein B-48-containing chylomicrons, deuterated cholest erol concentrations were moderate after the first meal (1.3 x 10(-4) mmol/L ), reached a maximum after the second meal (2.4 x 10(-4) mmol/L), and were still elevated after the third meal (1.7 x 10(-4) mmol/L). In plasma, LDL a nd HDL cholesterol enrichment in deuterated cholesterol was lower than in c hylomicrons and plateaued after 24-48 h. Estimates of newly secreted exogen ous deuterated cholesterol in chylomicrons indicate that 30.7%, 55.2%, and 14.1% of the total was secreted after the first, second, and third meals, r espectively. Conclusion: Ingested dietary cholesterol is secreted by the small intestine in chylomicrons into the circulation during greater than or equal to3 subs equent postprandial periods in healthy humans. This likely results from a c omplex multistep intestinal processing of cholesterol with dietary fat as a driving force.