| Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice. | |
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MedLine Citation:
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PMID: 19723664 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Scavenger receptor BI (SR-BI) is a selective uptake receptor for HDL cholesterol but is also involved in the catabolism of apolipoprotein (apo)B-containing lipoproteins. However, plasma levels of apoB-containing lipoproteins increase following hepatic SR-BI overexpression, suggesting that SR-BI not solely mediates their catabolism. We therefore tested the hypothesis that hepatic SR-BI impacts on VLDL production. On day 7 following adenovirus (Ad)-mediated overexpression of SR-BI, VLDL-triglyceride and VLDL-apoB production rates were significantly increased (P < 0.001), whereas VLDL production was significantly lower in SR-BI knockout mice compared with controls (P < 0.05). In mice injected with AdSR-BI, hepatic cholesterol content increased (P < 0.001), microsomal triglyceride transfer protein activity was higher (P < 0.01) and expression of sterol-regulatory element binding protein (SREBP)2 and its target genes was decreased (P < 0.01). Conversely, in SR-BI knockout mice, microsomal triglyceride transfer protein activity was lower and expression of SREBP2 target genes was increased (P < 0.01). Finally, we demonstrate in vitro in isolated primary hepatocytes as well as in vivo that cholesterol derived from HDL and taken up via SR-BI into the liver can be resecreted within VLDL. These data indicate that hepatic SR-BI expression is linked to VLDL production, and within liver, a metabolic shunt might exist that delivers HDL cholesterol, at least in part, to a pool from which cholesterol is mobilized for VLDL production. These results might have implications for HDL-based therapies against atherosclerotic cardiovascular disease, especially with SR-BI as target. |
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Authors:
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Harmen Wiersma; Niels Nijstad; Thomas Gautier; Jahangir Iqbal; Folkert Kuipers; M Mahmood Hussain; Uwe J F Tietge |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-01 |
Journal Detail:
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Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-16 Completed Date: 2010-05-07 Revised Date: 2011-07-25 |
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: 544-53 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins B / biosynthesis Carrier Proteins / metabolism Cholesterol, HDL / blood, metabolism, secretion Gene Knockout Techniques Humans Lipoproteins, VLDL / biosynthesis*, blood Liver / metabolism*, secretion Mice Mice, Inbred C57BL Scavenger Receptors, Class B / deficiency, genetics, metabolism* Triglycerides / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins B; 0/Carrier Proteins; 0/Cholesterol, HDL; 0/Lipoproteins, VLDL; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/Triglycerides; 0/microsomal triglyceride transfer protein |
| Comments/Corrections | |
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