THE MECHANISM OF CHOLESTEROL ABSORPTION

In reviewing the literature directly related to sterol absorption one is impressed by the very limited area of agreement. Most investigators agree that absorbed cholesterol is transported via the lymph, that bile is obligatory for absorption, and that a major portion of the cholesterol in lymph is in the esterified form.’-b There is also evidence both for and against the participation of pancreatic juice and esterification in the absorption process.6-12 There are three puzzling aspects of cholesterol absorption that cannot be explained on the basis of a direct transfer of cholesterol from the lumen of the intestine to lymph. These are: first, the appearance of fed cholesterol-4-CI4 in lymph for periods up to several days; second, the endogenous dilution of fed cholesterol-PCI4 in its transfer from the lumen to the lymph and, third, the poor absorption of cholesterol-4-C14 when large or small doses are fed. Recently Glover and his co-worker~~~~ l4 have postulated that cholesterol absorption takes place at a molecular level by way of a rapid exchange and transfer process between the lipoproteins of the cell membrane, organelles, and ground plasm. Endogenous dilution occurs due to interchange of the labeled cholesterol with inactive cholesterol on the lipoproteins. According to these workers, esterification acts in absorption only as an accelerating factor. Also, one explanation offered for the absorption of plant st9rols is based on the fact that these have a certain degree of a fh i ty for the acceptor lipoproteins that allow these sterols to participate in exchange reactions during passage across the mucosal cells. The mechanism proposed by Glover and his colleagues accounts neither for the obligatory requirement of bile nor for the appearance of labeled cholesterol in the lymph for periods up to several days after its feeding. in which cholesterol-PC14 and the lymph fistula animal have been used to study cholesterol absorption, it has been common practice to administer 1 to 3 mg. cholesterol-4-C14 dissolved in corn or cottonseed oil. In a fasted rat the amount of cholesterol appearing in the thoracic duct lymph during a 2Phour period is 8 to 10 mg.16* Is When fat alone is administered there is an increase of approximately 2 mg. in the lymph cholesterol level.16 Thus, the administration of small amounts of cholesterol-4-Cl4 (1 to 3 mg.) dissolved in fat does not produce a chemical increase in the lymph cholesterol over that normally expected from the feeding of fat alone. However, as demonstrated by several workers, the feeding of these amounts of cholesterol-PC14 is followed ,by the appearance of labeled cholesterol in lymph.4* 6 , 7-9 While this certainly demonstrates absorption of the labeled * The work reported in this paper was supported in part by research grants from the American Heart Association, Inc., New York, N. Y., and Grants H-1897 and H-2746 from the National Heart Institute, Public Health Service, Bethesda, Md.