Absorption of Cholesterol from a Micellar Solution: Intestinal Perfusion Studies in Man*

Abstract

Summary. The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-14C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained.Each of the components of the micelle was absorbed to a different extent during passage through the test segment of jejunum. Bile salt was not absorbed (mean, -3%), but micellar monoglyceride was rapidly hydrolyzed and absorbed almost completely (mean, 98%). Cholesterol radioactivity was absorbed to an intermediate extent (mean, 73%), and the absorption of chemically determined cholesterol (mean, 46%) indicated that much of the disappearance of radioactivity represented true absorption and not simple exchange.The specific activity of the perfused cholesterol fell during passage through the loop. This fall was interpreted as signifying the continuous addition of nonradioactive endogenous cholesterol by the test segment. However, the decrease in specific activity may also be considered to signify exchange, in that nonradioactive molecules entered the lumen as radioactive molecules were absorbed. Plant sterols appeared in the intestinal contents during the perfusion and must have been contributed by the perfused segment.The perfusate and samples taken from the upper and lower collection sites were examined by ultracentrifugation to define the physical state of cholesterol. It was found that cholesterol in the perfusate or upper collection site samples did not sediment, but that 23% of the cholesterol in the lower collection site samples was sedimentable (mean of three experiments); bile salt, as control, was not sedimentable. Solubility experiments in model systems showed that cholesterol possessed low solubility in bile salt solution; its solubility increased markedly and in linear proportion to the amount of

Targeted Depletion of Hepatic ACAT2-driven Cholesterol Esterification Reveals a Non-biliary Route for Fecal Neutral Sterol Loss

“…In fact, the non-biliary route of fecal sterol loss may play a substantial role in maintaining sterol balance, making up a large portion of fecal neutral sterol excretion in both mice (28) and man (29). To address the quantifiable importance of this pathway in mice, Plosch and colleagues (28) treated wild type and ABCA1-deficient mice with the synthetic LXR agonist T0901317 and quantified amounts dietary cholesterol, biliary cholesterol, and fecal cholesterol to get an estimate of this nonbiliary pathway.…”

“…Using micellar radiolabeled cholesterol and calculating specific activity changes, the authors concluded: "cholesterol was absorbed by, and in all probability, secreted by the test segment." This study estimated that ϳ44% of total fecal sterol output in the perfused intestinal test segment originated from endogenous sources (29). Most recently, Van der Velde and colleagues (30) using a mouse intestinal perfusion system demonstrated that plasma cholesterol can traverse the small intestine in a basolateral to apical direction in a process that is dependent on bile salt and phospholipid acceptors being present in the intestinal lumen (30).…”

Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols

“…Cows, for example, eat only foods that contain plant sterols, and yet their bodies contain cholesterol but not plant sterols. Investigations of such observations led to the discovery that plant sterols were excluded by the body, but could compete with bulk cholesterol for entry into the micelles formed during digestion, thus preventing dietary absorption of cholesterol [6,14,21,34,50,55,59]. Into this milieu of understanding, two key landmark observations led to a revolution in our current knowledge of how whole-body sterol balance may be achieved.…”

“…Based upon the response of patients with sitosterolemia to the drug ezetimibe, blocking NPC1L1 seems to lower plasma plant sterol levels and seems to improve symptoms and signs [52]. From studies involving mice as well as humans, the intestine can secrete cholesterol back into the lumen of the intestine [33,55]. It is possible that it may also be able to *Activation by stigmasterol in an adrenal cell line has also been demonstrated secrete noncholesterol sterols.…”

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“…the low aqueous concentration of fatty acid is compensated by absorption over a longer period from a larger absorption area (39). The available experimental evidence has nonetheless led to the consideration that fatty acids and other lipids even in the presence of bile salts are absorbed from the molecular dispersed aqueous solution (60). The explanation of this apparent discrepancy may be found in the importance of the so-called unstirred layer in lipid absorption.…”