Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo

• Published in: Journal of lipid research Vol. 49; no. 1; pp. 136 - 146
• Main Authors: Van Eck, Miranda, Hoekstra, Menno, Out, Ruud, Bos, I. Sophie T., Kruijt, J. Kar, Hildebrand, Reeni B., Van Berkel, Theo J.C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2008; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; Cholesterol, HDL - blood; Cholesterol, VLDL - blood; gene expression; hepatocytes; Hepatocytes - metabolism; Humans; Lipolysis; Lipoproteins, VLDL - blood; Lipoproteins, VLDL - metabolism; liver; Liver - metabolism; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; Mice; Mice, Knockout; mouse model; Rats; Receptors, LDL - metabolism; Scavenger Receptors, Class B - deficiency; Scavenger Receptors, Class B - metabolism; mouse model; liver; hepatocytes; gene expression
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M700355-JLR200

Scavenger receptor class B type I (SR-BI) functions as an HDL receptor that promotes the selective uptake of cholesteryl esters (CEs). The physiological role of SR-BI in VLDL metabolism, however, is largely unknown. SR-BI deficiency resulted in elevated VLDL cholesterol levels, both on chow diet and upon challenge with high-cholesterol diets. To specifically elucidate the role of SR-BI in VLDL metabolism, the plasma clearance and hepatic uptake of 125I-β-VLDL were studied in SR-BI+/+ and SR-BI−/− mice. At 20 min after injection, 66 ± 2% of the injected dose was taken up by the liver in SR-BI+/+ mice, as compared with only 22 ± 4% (P = 0.0007) in SR-BI−/− mice. In vitro studies established that the Bmax of 125I-β-VLDL binding was reduced from 469 ± 30 ng/mg in SR-BI+/+ hepatocytes to 305 ± 20 ng/mg (P = 0.01) in SR-BI−/− hepatocytes. Both in vivo and in vitro, limited to no selective uptake of CEs from β-VLDL was found. Interestingly, HDL effectively competed for the association of β-VLDL in the presence as well as in the absence of SR-BI, indicating a second common recognition site. In conclusion, SR-BI plays an important physiological role in the metabolism of VLDL (remnants).