Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice

Abstract

The recent identification of the aberrant transport proteins ABCG5 and ABCG8 resulting in sitosterolemia suggests that intestinal uptake of cholesterol is an unselective process, and that discrimination between cholesterol and plant sterols takes place at the level of sterol efflux from the enterocyte. Although plant sterols are structurally very similar to cholesterol, differing only in their side chain length, they are absorbed from the intestine to a markedly lower extent. In order to further evaluate the process of discrimination, three different sterols (cholesterol, campesterol, sitosterol) and their corresponding 5 ␣ -stanols (cholestanol, campestanol, sitostanol) were compared concerning their concentration in the proximal small intestine, in serum, and in bile after a single oral dose of deuterated compounds. The data obtained support the hypothesis that i ) the uptake of sterols and stanols is an extremely rapid process, ii ) discrimination probably takes place on the level of reverse transport back into the gut lumen, iii ) plant stanols are taken up, but not absorbed to a measurable extent, and iv ) the process of discrimination probably also exists at the level of biliary excretion. The range of structural alterations that decrease intestinal absorption and increase biliary excretion is: 1 ) campesterol, 2 ) cholestanol-sitosterol, and 3 ) campestanol-sitostanol. Investigators have been intrigued for more than a decade with the concept that there is a protein-mediated transport system responsible for intestinal uptake of cholesterol (1). The recent identification of the molecular defects underlying phytosterolemia (2, 3) and the lines of evidence supporting the existence of a specific transport protein located in the brush border membrane that possibly mediates intestinal sterol absorption (4-6) has shed new light on the cellular transport of cholesterol and plant sterols. Based on the characterization of sterol uptake in brush border membranes, it is currently hypothesized that the process of intestinal sterol uptake is protein mediated and that the pumping of sterols from the intestine into the enterocyte is unselective. In phytosterolemia, a rare autosomal recessive disorder caused by mutations in the tandem ABC genes, either ABCG5 or ABCG8, affected individuals hyperabsorb and retain not only cholesterol but also plant sterols (7-11). Consequently, it is hypothesized that the ABC transporters G5 and G8 are able to discriminate between cholesterol and other sterols. They are pumping the noncholesterol sterols out of the intestinal cell back into the gut lumen and also into bile, and they are differentiating between the side-chain length and probably also between the stereoselective 5 ␣ saturation of the ⌬ 5 double bond to stanols (12, 13).Plant sterols are structurally related to cholesterol and differ in their chemical structure only due to the presence of an additional methyl (campesterol) or ethyl (sitosterol) group at the C-24 position of the side chain. Stanols differ from the corre...

Missense Mutation inAbcg5in SHRSP Rats Does Not Accelerate Intestinal Absorption of Plant Sterols: Comparison with Wistar Rats

“…9) They thought that since sitosterol was rapidly excreted from intestinal cells to the intestinal lumen, the ratios of sitosterol/cholesterol decreased. However, our present results do not support this.…”

“…Igel et al administered various sterols and stanols as an oil suspension to mouse stomach. 9) The incorporated plant sterol and cholesterol at an early stage after administration were thought to be extremely low in quantity, because almost all of the suspension was assumed to be in the stomach. Hence, we infused a bile salt micelle containing sitosterol and cholesterol into the duodenum.…”

“…6) Igel et al have proposed that plant sterols are incorporated into intestinal cells and then are secreted to the intestinal lumen via ABCG5 and ABCG8. 9) They suggested that secretion of plant sterols into the intestinal lumen by ABCG5 and ABCG8 is an important determinant of intestinal absorption of sterols. In the present study, we also evaluated to determine whether incorporation of sitosterol and cholesterol into intestinal cells is accelerated in SHRSP rats as compared with Wistar rats.…”

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

“…They were cultured in 75 cm 2 Falcon flasks in Dulbecco's modified Eagle's medium (DMEM) containing 25 mM glucose and supplemented with 10% heat-inactivated (561C) horse serum, 100 U/ml penicillin, 100 mg/ml streptomycin, 1% nonessential amino acids (Gibco, Invitrogen Corp., Cergy Pontoise, France). Cells were incubated at 371C in a humidified atmosphere with 5% CO 2 and subcultured to preconfluency after trypsinization (0.5% trypsin/2.6 mM EDTA).…”

“…They are structural analogues of cholesterol. Numerous laboratory studies focused on their potential to reduce cholesterol absorption by the small intestine, [1][2][3][4] and cholesterol uptake by LDL. [5][6][7] In addition, it was reported that phytosterols prevent coronary heart disease, 8 and cardiovascular risks.…”