| Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport. | |
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MedLine Citation:
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PMID: 18599737 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutral cholesteryl ester hydrolase (CEH)-mediated hydrolysis of cellular cholesteryl esters (CEs) is required not only to generate free cholesterol (FC) for efflux from macrophages but also to release FC from lipoprotein-delivered CE in the liver for bile acid synthesis or direct secretion into the bile. We hypothesized that hepatic expression of CEH would regulate the hydrolysis of lipoprotein-derived CE and enhance reverse cholesterol transport (RCT). Adenoviral-mediated CEH overexpression led to a significant increase in bile acid output. To assess the role of hepatic CEH in promoting flux of cholesterol from macrophages to feces, cholesterol-loaded and [3H]cholesterol-labeled J774 macrophages were injected intraperitoneally into mice and the appearance of [3H]cholesterol in gallbladder bile and feces over 48 h was quantified. Mice overexpressing CEH had significantly higher [3H]cholesterol radiolabel in bile and feces, and it was associated with bile acids. This CEH-mediated increased movement of [3H]cholesterol from macrophages to bile acids and feces was significantly attenuated in SR-BI(-/-) mice. These studies demonstrate that similar to macrophage CEH that rate-limits the first step, hepatic CEH regulates the last step of RCT by promoting the flux of cholesterol entering the liver via SR-BI and increasing hepatic bile acid output. |
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Authors:
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Bin Zhao; Jingmei Song; Shobha Ghosh |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-03 |
Journal Detail:
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Title: Journal of lipid research Volume: 49 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-15 Completed Date: 2008-10-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 2212-7 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Bile / metabolism Bile Acids and Salts / metabolism Biological Transport Cell Line Cholesterol / metabolism* Cholesterol, HDL / metabolism Feces Gene Expression Gene Expression Regulation, Enzymologic Humans Lipoproteins / blood Liver / enzymology, metabolism* Macrophages / metabolism Mice Sterol Esterase / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Cholesterol, HDL; 0/Lipoproteins; 57-88-5/Cholesterol; EC 3.1.1.13/Sterol Esterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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