HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400361-JLR200v1 46/6/1172    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Out, R. Articles by Van Berkel, T. J. C. Search for Related Content PubMed PubMed Citation Articles by Out, R. Articles by Van Berkel, T. J. C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 1172-1181, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice

Ruud Out^1,*, 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^* and Theo J. C. Van Berkel^*

^* Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The Netherlands
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536

Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400361-JLR200

¹ To whom correspondence should be addressed. e-mail: r.out{at}lacdr.leidenuniv.nl

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 x 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.

Abbreviations: apoA-I, apolipoprotein A-I; BSEP, bile salt export pump; CE, cholesteryl ester; CM, chylomicron; HPRT, hypoxanthine guanine phosphoribosyl transferase; LDLr, low density lipoprotein receptor; LRP1, LDLr-related protein 1; MTP, microsomal triglyceride transfer protein; pfu, plaque-forming units; PL, phospholipid; SR-BI, scavenger receptor class B type I; TG, triglyceride; 36B4, acidic ribosomal phosphoprotein PO

Supplementary key words liver • triglyceride • postprandial response • gene expression

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Hu, C. C. van der Hoogt, S. M. S. Espirito Santo, R. Out, K. E. Kypreos, B. J. M. van Vlijmen, T. J. C. Van Berkel, J. A. Romijn, L. M. Havekes, K. W. van Dijk, et al. The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI J. Lipid Res., July 1, 2008; 49(7): 1553 - 1561. [Abstract] [Full Text] [PDF]

				N. Densupsoontorn, Y. A. Carpentier, R. Racine, F. M. Murray, T. Seo, R. Ramakrishnan, and R. J. Deckelbaum CD36 and Proteoglycan-Mediated Pathways for (n-3) Fatty Acid Enriched Triglyceride-Rich Particle Blood Clearance in Mouse Models In Vivo and in Peritoneal Macrophages In Vitro J. Nutr., February 1, 2008; 138(2): 257 - 261. [Abstract] [Full Text] [PDF]

				R. Out, W. Jessup, W. Le Goff, M. Hoekstra, I. C. Gelissen, Y. Zhao, L. Kritharides, G. Chimini, J. Kuiper, M. J. Chapman, et al. Coexistence of Foam Cells and Hypocholesterolemia in Mice Lacking the ABC Transporters A1 and G1 Circ. Res., January 4, 2008; 102(1): 113 - 120. [Abstract] [Full Text] [PDF]

				C. C. van der Hoogt, W. de Haan, M. Westerterp, M. Hoekstra, G. M. Dallinga-Thie, J. A. Romijn, H. M. G. Princen, J. W. Jukema, L. M. Havekes, and P. C. N. Rensen Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression J. Lipid Res., August 1, 2007; 48(8): 1763 - 1771. [Abstract] [Full Text] [PDF]

				T. J. F. Nieland, J. T. Shaw, F. A. Jaipuri, Z. Maliga, J. L. Duffner, A. N. Koehler, and M. Krieger Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI J. Lipid Res., August 1, 2007; 48(8): 1832 - 1845. [Abstract] [Full Text] [PDF]

				T. Tanaka, J. Delgado-Lista, J. Lopez-Miranda, F. Perez-Jimenez, C. Marin, P. Perez-Martinez, P. Gomez, and J. M. Ordovas Scavenger Receptor Class B Type I (SCARB1) c.1119C>T Polymorphism Affects Postprandial Triglyceride Metabolism in Men J. Nutr., March 1, 2007; 137(3): 578 - 582. [Abstract] [Full Text] [PDF]

				H. Yu, W. Zhang, P. G. Yancey, M. J. Koury, Y. Zhang, S. Fazio, and M. F. Linton Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor-Class BI Double-Knockout Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 150 - 156. [Abstract] [Full Text] [PDF]