E. C. Trout

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.

Specific function of bile salts in cholesterol absorption.

Summary Entrance of cholesterol-4-C14 into the free cholesterol pool of mucosa and its subsequent transfer to the lymph requires the presence of a specific type of bile salt. This process does not require the presence of dietary fatty acid. It is suggested that free cholesterol in the lumen of the intestine complexes with bile salt which then enters the free cholesterol pool of mucosa.

Electrolyte Changes in Ileal Contents and in Feces during Restriction of Dietary Sodium with and without the Administration of Cation-Exchange Resin

Sodium and potassium levels of the contents of the terminal ileum and feces were determined for four dogs at different dietary sodium intakes, both before and during administration of a carboxylic cation-exchange resin. With restriction of dietary sodium, there was more sodium bound by the resin in the terminal ileum than was provided by the diet. There was considerable conservation of sodium in the upper gastrointestinal tract, but the colon always absorbed a major part of the sodium presented to it. During resin administration with very low sodium diets there was more sodium in the feces than in the diets.

Effect of dietary fat and fatty acid on fecal excretion of a calcium oleate phosphate complex.

Summary The excretion of a calcium oleate-phosphate lipid complex in the feces of rats was studied under various dietary conditions. Diets containing 25% of either olive oil. corn oil. hydrogenated soybean oil, palmitic acid or oleic acid were compared with a fat-free basal diet. Oleic acid was approximately 70 times more effective in stimulating formation of lipid than either corn oil or olive oil. Palmitic acid had a very slight effect, whereas hydrogenated soybean oil had no effect. The absorption of oleic acid was much lower than that of palmitic acid, corn oil or olive oil, perhaps due to the formation of the lipid. The significance of the fecal lipid is discussed.

Absorption of H3-β-Sitosterol in the Lymph Fistula Rat.∗

Summary Administration of 44 mg of H3-β-sitosterol to lymph fistula rats and analysis of feces, intestinal contents, intestine, and lymph gave the following results: (1) balance data indicated approximately 40% absorption in 48 hours, (2) there was increased fecal excretion of cholesterol and related sterols, (3) there was considerable uptake of H3-β-sitosterol by the intestinal wall, but essentially no transfer into the lymph. Explanations for the apparent disappearance of H3-β-sitosterol are discussed.

Influence of H3-β-Sitosterol on Sterol Excretion.∗

Summary An increased fecal excretion of cholesterol and related sterols followed the administration of H3-β-sitosterol to rats receiving cholesterol-free emulsions containing bile salt and fatty acid. Approximately 53% of the administered labeled βT-sitosterol was not recovered in the feces. Our study provides additional evidence that plant sterols are absorbed in the same manner as cholesterol and thereby compete with cholesterol for the sterol absorptive mechanism.

Labeling of intestinal and lymph cholesterol after administration of tracer doses of cholesterol-4-C14.

Summary Small doses of fed cholesterol-4-C14 lead to labeling of cholesterol fractions of mucosa and lymph without increase in level or turnover rate of free cholesterol pool of the mucosa or in amount of cholesterol in lymph. Feeding tracer dose with sodium taurocholate and oleic acid increases the turnover rate of pool which leads to an increased amount of labeled and unlabeled cholesterol in lymph.