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Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1

Published online by Cambridge University Press:  08 March 2007

Laura Calpe-Berdiel
Affiliation:
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, 08025 BarcelonaSpain Institut de Recerca, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
Joan Carles Escolà-Gil*
Affiliation:
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, 08025 BarcelonaSpain Institut de Recerca, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
Francisco Blanco-Vaca
Affiliation:
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, 08025 BarcelonaSpain
*
*Corresponding author: fax +34 93 2919196, email jescola@hsp.santpau.es
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Abstract

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An increased activity of ATP-binding cassette transporter (ABC) A1 has been proposed as a mechanism underlying the hypocholesterolaemic effect of phytosterols. In the present study, ABCA1-deficient mice (ABCA1−/− mice) were used to examine the involvement of the ABCA1 in the reduction of intestinal cholesterol absorption in response to a phytosterol-enriched diet. A decrease in intestinal cholesterol absorption of 39 and 35% was observed after phytosterol treatment in ABCA1+/+ mice and in ABCA1−/− mice, respectively. No statistically significant changes in plasma lipoprotein profile or in intestinal ABCG5, ABCG8 and Niemann-Pick C1-Like 1 gene expression levels were found when phytosterol-treated ABCA1−/− mice and untreated ABCA1−/− mice were compared. We conclude that phytosterol inhibition of cholesterol absorption in mice is independent of ABCA1

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Altmann, SW, Davis, HR Jr, Zhu, LJ et al. 2004 Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303, 12011204.CrossRefGoogle ScholarPubMed
Brousseau, M 2003 ATP-binding cassette transporter A1, fatty acids, and cholesterol absorption. Curr Opin Lipidol 14, 3540.CrossRefGoogle ScholarPubMed
Calpe-Berdiel, L, Escola-Gil, JC, Ribas, VNavarro-Sastre, A, Garces-Garces, J & Blanco-Vaca, FChanges in intestinal and liver global gene expression in response to a phytosterol-enriched diet. Atherosclerosis 2005 181, 7585.CrossRefGoogle ScholarPubMed
Davies, JP, Scott, C, Oishi, KLiapis, A & Ioannou, YA 2005 Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J Biol Chem 280, 1271012720.CrossRefGoogle ScholarPubMed
de Jong, A, Plat, J & Mensink, RP 2003 Metabolic effects of plant sterols and stanols (review). J Nutr Biochem 14, 362369.CrossRefGoogle ScholarPubMed
Drobnik, W, Lindenthal, B, & Lieser, B et al. 2001 ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology 120, 12031211.CrossRefGoogle ScholarPubMed
Duan, LP, Wang, HH & Wang, DQJ Lipid Res. Cholesterolabsorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters ABCG5 and ABCG8 in mice 2004 45 13121323.Google Scholar
Escola-Gil, JC, Julve, J, Marzal-Casacuberta, A, Ordonez-Llanos, J, GonzalezA-Sastre, F & Blanco-Vaca, F 2000 Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia. J Lipid Res 41 13281338.CrossRefGoogle ScholarPubMed
Escola-Gil, JC, Julve, J, Marzal-Casacuberta, A, Ordonez-Llanos, J, Gonzalez-Sastre, F & Blanco-Vaca, F 2001 ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance. J Lipid Res 42, 241248.CrossRefGoogle ScholarPubMed
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) JAMA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol inAdults Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP)Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) 285, 24862497.Google Scholar
Field, FJ, Born, E & Mathur, SN 2004 Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick C1-Like 1 protein gene expression. J Lipid Res 45, 22522259.CrossRefGoogle ScholarPubMed
Groen, AK, Bloks, VW, Bandsma, RH, Ottenhoff, R, Chimini, G & Kuipers, F 2001 Hepatobiliary cholesterol transport is not impaired in ABCA1-null mice lacking HDL. J Clin Invest 108, 843850.CrossRefGoogle Scholar
Hayes, KC, Pronczuk, AWijendran, V & Beer, M 2005 Free phytosterols facilitate excretion of endogenous cholesterol in gerbils. J Nutr Biochem 16 305311.CrossRefGoogle ScholarPubMed
Joyce, C, Freeman, L, Brewer, HB Jr & Santamarina-Fojo, S 2003 Study of ABCA1 function in transgenic mice. Arterioscler Thromb Vasc Biol 23, 965971.CrossRefGoogle ScholarPubMed
Kaneko, E, Matsuda, M, Yamada, Y, Tachibana, Y, Shimomura, I & Makishima, M 2003 Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J Biol Chem 278, 3609136098.CrossRefGoogle ScholarPubMed
McNeish, J, Aiello, RJGuyot, D et al. 2000 High density lipoprotein deficiency and foam cell accumulation inmice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci USA 97, 42454250.CrossRefGoogle Scholar
Mulligan, JD, Flowers, MT, Tebon, A, Bitgood, JJ, Wellington, C, Hayden, MR & Attie, AD 2003 ABCA1 is essential for efficient basolateral cholesterol efflux during the absorption of dietary cholesterol in chickens. J Biol Chem 278, 1335613366.CrossRefGoogle ScholarPubMed
Ohama, T, Hirano, KZhang, Z et al. 2002 Dominant expression of ATPbinding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands. Biochem Biophys Res Commun 296, 625630.CrossRefGoogle ScholarPubMed
Plat, J & Mensink, RP 2002 Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J 16, 12481253.CrossRefGoogle Scholar
Plat, J, Nichols, JA & Mensink, RP 2005 Plantsterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J Lipid Res 46, 24682476.CrossRefGoogle ScholarPubMed
Plat, J, van Onselen, EN, van Heugten, MM & Mensink, RP 2000 Effects on serum lipids, lipoproteins and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters. Eur J Clin Nutr 54, 671677.CrossRefGoogle ScholarPubMed
Plosch, T, Kok, T, Bloks, VW, Smit, MJ, Havinga, R, Chimini, Ghimini, Groen, AK & Kuipers, F 2002 Increased hepatobiliary and fecal cholesterol excretion upon activation of the liver X receptor is independent of ABCA1. J Biol Chem 277, 3387033877.CrossRefGoogle ScholarPubMed
Repa, JJ, Dietschy, JM & Turley, SD 2002 Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte. J Lipid Res 43, 18641874.CrossRefGoogle ScholarPubMed
Sahoo, D, Trischuk, TC, Chan, T, Drover, VA, Ho, S, Chimini, G, Agellon, LB, Agnihotri, R, Francis, GA & Lehner, R 2004 ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes. J Lipid Res 45, 11221131.CrossRefGoogle ScholarPubMed
Sehayek, E 2003 Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences. J Lipid Res 44, 20302038.CrossRefGoogle ScholarPubMed
Sudhop, T, Lutjohann, D & von Bergmann, KSterol transporters:targets of natural sterols and new lipid lowering drugs.Pharmacol Ther 2005 105, 333341.CrossRefGoogle ScholarPubMed
Temel, RE, Lee, RG, Kelley, KL, Davis, MA, Shah, R, Sawyer, JK, Wilson, MD & Rudel, LL 2005 Intestinal cholesterol absorption is substantially reduced in mice deficient in both ATP-binding cassette transporter A1 (ABCA1) and acyl-CoA:cholesterol O-acyltransferase 2 (ACAT2). J Lipid Res 46, 24232431.CrossRefGoogle Scholar
Timmins, JM, Lee, JY, Boudyguina, E et al. 2005 Targeted inactivation of hepatic ABCA1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 115, 13331342.CrossRefGoogle ScholarPubMed