| Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects. | |
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MedLine Citation:
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PMID: 16179600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 )alpha plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17beta-estradiol-releasing pellets at 0, 3, or 6 mug/day and antiestrogenic ICI 182,780 at 125 microg/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 ERalpha pathway, which can be fully abolished by the antagonist. We conclude that ERalpha 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. |
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Authors:
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Li-Ping Duan; Helen H Wang; Akira Ohashi; David Q-H Wang |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2005-09-22 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 290 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-12 Completed Date: 2006-03-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G269-76 Citation Subset: IM |
Affiliation:
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Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., DA 601, Boston, MA 02215, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
physiology* Aging / physiology* Animals Cholesterol, Dietary / pharmacokinetics* Diet Estrogen Antagonists / pharmacology Estrogens / physiology Gastrointestinal Transit / physiology Intestinal Absorption / physiology* Intestine, Small / metabolism Lipoproteins / genetics, physiology* Membrane Transport Proteins / genetics, physiology* Mice Mice, Inbred AKR Mice, Inbred C57BL Receptors, Estrogen / drug effects Reverse Transcriptase Polymerase Chain Reaction Sex Characteristics Species Specificity |
| Grant Support | |
ID/Acronym/Agency:
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DK-54012/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ABCG5 protein, mouse; 0/ABCG8 protein, mouse; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, Dietary; 0/Estrogen Antagonists; 0/Estrogens; 0/Lipoproteins; 0/Membrane Transport Proteins; 0/Npc1l1 protein, mouse; 0/Receptors, Estrogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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