Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo

Journal of Lipid Research

Theo J.C. Van Berkel¹  Menno Hoekstra¹  I. Sophie T. Bos¹  Reeni B. Hildebrand¹  Miranda Van Eck¹  Ruud Out¹  J. Kar Kruijt¹ 

[1] Divison of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands;

关键词: liver;    hepatocytes;    gene expression;    mouse model;   

DOI  :  

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown