Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520346447 |
| _version_ | 1819077236382236672 |
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| author | Bin Zhao Jingmei Song Shobha Ghosh |
| author_facet | Bin Zhao Jingmei Song Shobha Ghosh |
| author_sort | Bin Zhao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:53:59Z |
| format | Article |
| id | doaj.art-6ab84baad4754a29b3a41560b389a0bb |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:53:59Z |
| publishDate | 2008-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6ab84baad4754a29b3a41560b389a0bb2022-12-21T18:53:40ZengElsevierJournal of Lipid Research0022-22752008-10-01491022122217Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transportBin Zhao0Jingmei Song1Shobha Ghosh2Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Neutral 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.http://www.sciencedirect.com/science/article/pii/S0022227520346447liverbile acid excretionlipoprotein cholesterol removalselective uptakeHDL cholesteryl esters |
| spellingShingle | Bin Zhao Jingmei Song Shobha Ghosh Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport Journal of Lipid Research liver bile acid excretion lipoprotein cholesterol removal selective uptake HDL cholesteryl esters |
| title | Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| title_full | Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| title_fullStr | Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| title_full_unstemmed | Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| title_short | Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| title_sort | hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport |
| topic | liver bile acid excretion lipoprotein cholesterol removal selective uptake HDL cholesteryl esters |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520346447 |
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