Document Detail


Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice.
MedLine Citation:
PMID:  19723664     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Harmen Wiersma; Niels Nijstad; Thomas Gautier; Jahangir Iqbal; Folkert Kuipers; M Mahmood Hussain; Uwe J F Tietge
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-01
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-16     Completed Date:  2010-05-07     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  544-53     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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:
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
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