| Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. | |
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MedLine Citation:
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PMID: 20674863 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several steps of the HDL-mediated reverse cholesterol transport (RCT) are transcriptionally regulated by the nuclear receptors LXRs in the macrophages, liver, and intestine. Systemic LXR activation via synthetic ligands induces RCT but also causes increased hepatic fatty acid synthesis and steatosis, limiting the potential therapeutic use of LXR agonists. During the last few years, the participation of the intestine in the control of RCT has appeared more evident. Here we show that while hepatic-specific LXR activation does not contribute to RCT, intestinal-specific LXR activation leads to decreased intestinal cholesterol absorption, improved lipoprotein profile, and increased RCT in vivo in the absence of hepatic steatosis. These events protect against atherosclerosis in the background of the LDLR-deficient mice. Our study fully characterizes the molecular and metabolic scenario that elects the intestine as a key player in the LXR-driven protective environment against cardiovascular disease. |
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Authors:
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Giuseppe Lo Sasso; Stefania Murzilli; Lorena Salvatore; Ilenia D'Errico; Michele Petruzzelli; Paola Conca; Zhao-Yan Jiang; Laura Calabresi; Paolo Parini; Antonio Moschetta |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell metabolism Volume: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-11-22 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 187-93 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / prevention & control* Biological Transport Cholesterol / metabolism* Intestines / metabolism* Mice Mice, Inbred C57BL Mice, Transgenic Orphan Nuclear Receptors / genetics, metabolism* Receptors, LDL / deficiency, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GGP08259//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Orphan Nuclear Receptors; 0/Receptors, LDL; 0/liver X receptor; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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