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: 290/2/G269    most recent 00172.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Duan, L.-P. Articles by Wang, D. Q.-H. Search for Related Content PubMed PubMed Citation Articles by Duan, L.-P. Articles by Wang, D. Q.-H.

LIVER AND BILIARY TRACT

Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects

Department of Medicine, Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston, Massachusetts

Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER ) plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17-estradiol-releasing pellets at 0, 3, or 6 µg/day and antiestrogenic ICI 182,780 at 125 µg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette (Abc)g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ER pathway, which can be fully abolished by the antagonist. We conclude that ER activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.

bile; bile salt; biliary secretion; chylomicron; genetics; intestinal lipid uptake; lymph; micelle; nutrition; phospholipid

This article has been cited by other articles:

				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]