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

Abstract

Background: The process of intestinal absorption and chylomicron resecretion of dietary cholesterol in humans is poorly understood. Objective: The present study aimed to test the hypothesis that dietary cholesterol ingested during a given meal is resecreted into chylomicrons (and plasma) 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 cholesterol was present in the first test meal only, enabling its specific determination with use of gas chromatography-mass spectrometry. Chylomicrons, LDL, and HDL were isolated and lipids were quantified. Results: In apolipoprotein B-48-containing chylomicrons, deuterated cholesterol concentrations were moderate after the first meal (1.3 × 10-4 mmol/L), reached a maximum after the second meal (2.4 × 10-4 mmol/L), and were still elevated after the third meal (1.7 × 10-4 mmol/L). In plasma, LDL and HDL cholesterol enrichment in deuterated cholesterol was lower than in chylomicrons and plateaued after 24-48 h. Estimates of newly secreted exogenous 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, respectively. Conclusion: Ingested dietary cholesterol is secreted by the small intestine in chylomicrons into the circulation during ≥3 subsequent postprandial periods in healthy humans. This likely results from a complex multistep intestinal processing of cholesterol with dietary fat as a driving force.