Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice
The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of HDL cholesteryl esters is well established. In SR-BI-deficient mice, we recently observed a delayed postprandial triglyceride (TG) response, suggesting an additional role for SR-BI in facilitating chylomic...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520330224 |
| _version_ | 1818920514479980544 |
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| author | Ruud Out Menno Hoekstra Saskia C.A. de Jager Paula de Vos Deneys R. van der Westhuyzen Nancy R. Webb Miranda Van Eck Eric A.L. Biessen Theo J.C. Van Berkel |
| author_facet | Ruud Out Menno Hoekstra Saskia C.A. de Jager Paula de Vos Deneys R. van der Westhuyzen Nancy R. Webb Miranda Van Eck Eric A.L. Biessen Theo J.C. Van Berkel |
| author_sort | Ruud Out |
| collection | DOAJ |
| description | The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of HDL cholesteryl esters is well established. In SR-BI-deficient mice, we recently observed a delayed postprandial triglyceride (TG) response, suggesting an additional role for SR-BI in facilitating chylomicron (CM) metabolism. Here, we assessed the effect of adenovirus-mediated hepatic overexpression of SR-BI (Ad.SR-BI) in C57BL/6J mice on serum lipids and CM metabolism. Infection of 5 × 108 plaque-forming units per mouse of Ad.SR-BI significantly decreases serum cholesterol (>90%), phospholipids (>90%), and TG levels (50%), accompanied by a 41.4% reduction (P < 0.01) in apolipoprotein B-100 levels. The postprandial TG response is 2-fold lower in mice treated with Ad.SR-BI compared with control mice (area under the curve = 31.4 ± 2.4 versus 17.7 ± 3.2; P < 0.05). Hepatic mRNA expression levels of genes known to be involved in serum cholesterol and TG clearance are unchanged and thus could not account for the decreased plasma TG levels and the change in postprandial response.We conclude that overexpression of SR-BI accelerates CM metabolism, possibly by mediating the initial capture of CM remnants by the liver, whereby the subsequent internalization can be exerted by additional receptor systems such as the LDL receptor (LDLr) and LDLr-related protein 1. |
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| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T01:22:58Z |
| publishDate | 2005-06-01 |
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| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-33768369f3594264913e5d0d317ff6e02022-12-21T19:58:21ZengElsevierJournal of Lipid Research0022-22752005-06-0146611721181Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J miceRuud Out0Menno Hoekstra1Saskia C.A. de Jager2Paula de Vos3Deneys R. van der Westhuyzen4Nancy R. Webb5Miranda Van Eck6Eric A.L. Biessen7Theo J.C. Van Berkel8To whom correspondence should be addressed.; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDivision of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDivision of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDivision of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDepartment of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDivision of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsDivision of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The NetherlandsThe function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of HDL cholesteryl esters is well established. In SR-BI-deficient mice, we recently observed a delayed postprandial triglyceride (TG) response, suggesting an additional role for SR-BI in facilitating chylomicron (CM) metabolism. Here, we assessed the effect of adenovirus-mediated hepatic overexpression of SR-BI (Ad.SR-BI) in C57BL/6J mice on serum lipids and CM metabolism. Infection of 5 × 108 plaque-forming units per mouse of Ad.SR-BI significantly decreases serum cholesterol (>90%), phospholipids (>90%), and TG levels (50%), accompanied by a 41.4% reduction (P < 0.01) in apolipoprotein B-100 levels. The postprandial TG response is 2-fold lower in mice treated with Ad.SR-BI compared with control mice (area under the curve = 31.4 ± 2.4 versus 17.7 ± 3.2; P < 0.05). Hepatic mRNA expression levels of genes known to be involved in serum cholesterol and TG clearance are unchanged and thus could not account for the decreased plasma TG levels and the change in postprandial response.We conclude that overexpression of SR-BI accelerates CM metabolism, possibly by mediating the initial capture of CM remnants by the liver, whereby the subsequent internalization can be exerted by additional receptor systems such as the LDL receptor (LDLr) and LDLr-related protein 1.http://www.sciencedirect.com/science/article/pii/S0022227520330224livertriglyceridepostprandial responsegene expression |
| spellingShingle | Ruud Out Menno Hoekstra Saskia C.A. de Jager Paula de Vos Deneys R. van der Westhuyzen Nancy R. Webb Miranda Van Eck Eric A.L. Biessen Theo J.C. Van Berkel Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice Journal of Lipid Research liver triglyceride postprandial response gene expression |
| title | Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice |
| title_full | Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice |
| title_fullStr | Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice |
| title_full_unstemmed | Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice |
| title_short | Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice |
| title_sort | adenovirus mediated hepatic overexpression of scavenger receptor class b type i accelerates chylomicron metabolism in c57bl 6j mice |
| topic | liver triglyceride postprandial response gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520330224 |
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