HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M300042-JLR200v1 44/11/2049    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knight, B. L. Articles by Gibbons, G. F. Search for Related Content PubMed PubMed Citation Articles by Knight, B. L. Articles by Gibbons, G. F. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 2049-2058, November 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Inhibition of cholesterol absorption associated with a PPAR-dependent increase in ABC binding cassette transporter A1 in mice

Brian L. Knight^1,*, Dilip D. Patel^*, Sandy M. Humphreys, David Wiggins and Geoffrey F. Gibbons

^* Lipoprotein Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 ONN, UK
Metabolic Research Laboratory, Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK

¹ To whom correspondence should be addressed. e-mail: brian.knight{at}csc.mrc.ac.uk

Dietary supplementation with the peroxisome proliferator-activated receptor (PPAR) ligand WY 14,643 gave rise to a 4- to 5-fold increase in the expression of mRNA for the ATP binding cassette transporter A1 (ABCA1) in the intestine of normal mice. There was no effect in the intestine of PPAR-null mice. Consumption of a high-cholesterol diet also increased intestinal ABCA1 expression. The effects of WY 14,643 and the high-cholesterol diet were not additive. WY 14,643 feeding reduced intestinal absorption of cholesterol in the normal mice, irrespective of the dietary cholesterol concentration, and this resulted in lower diet-derived cholesterol and cholesteryl ester concentrations in plasma and liver. At each concentration of dietary cholesterol, there was a similar significant inverse correlation between intestinal ABCA1 mRNA content and the amount of cholesterol absorbed. The fibrate-induced changes in the intestines of the normal mice were accompanied by an increased concentration of the mRNA encoding the sterol-regulatory element binding protein-1c gene (SREBP-1c), a known target gene for the oxysterol receptor liver X receptor (LXR). There was a correlation between intestinal ABCA1 mRNA and SREBP-1c mRNA contents, but not between SREBP-1c mRNA content and cholesterol absorption.

These results suggest that PPAR influences cholesterol absorption through modulating ABCA1 activity in the intestine by a mechanism involving LXR.

Supplementary key words intestine • sterol-regulatory element binding protein • liver X receptor • peroxisome proliferator-activated receptor- null mice • -3 unsaturated fatty acid

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. M. de Vogel-van den Bosch, N. J. W. de Wit, G. J. E. J. Hooiveld, H. Vermeulen, J. N. van der Veen, S. M. Houten, F. Kuipers, M. Muller, and R. van der Meer A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1171 - G1180. [Abstract] [Full Text] [PDF]

				M. A. Valasek, S. L. Clarke, and J. J. Repa Fenofibrate reduces intestinal cholesterol absorption via PPAR{alpha}-dependent modulation of NPC1L1 expression in mouse J. Lipid Res., December 1, 2007; 48(12): 2725 - 2735. [Abstract] [Full Text] [PDF]

				J. Shimakura, T. Terada, H. Saito, T. Katsura, and K.-i. Inui Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor {alpha} Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G851 - G856. [Abstract] [Full Text] [PDF]

				F. Briand, S. Serisier, M. Krempf, B. Siliart, T. Magot, K. Ouguerram, and P. Nguyen Atorvastatin Increases Intestinal Cholesterol Absorption in Dogs J. Nutr., July 1, 2006; 136(7): 2034S - 2036S. [Full Text] [PDF]

				J. S. Moffit, L. M. Aleksunes, J. M. Maher, G. L. Scheffer, C. D. Klaassen, and J. E. Manautou Induction of Hepatic Transporters Multidrug Resistance-Associated Proteins (Mrp) 3 and 4 by Clofibrate Is Regulated by Peroxisome Proliferator-Activated Receptor {alpha} J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 537 - 545. [Abstract] [Full Text] [PDF]

				J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]

				S. K. Noh and S. I. Koo Milk Sphingomyelin Is More Effective than Egg Sphingomyelin in Inhibiting Intestinal Absorption of Cholesterol and Fat in Rats J. Nutr., October 1, 2004; 134(10): 2611 - 2616. [Abstract] [Full Text] [PDF]