Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo.
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 (125)I-beta-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 B(max) of (125)I-beta-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 beta-VLDL was found. Interestingly, HDL effectively competed for the association of beta-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).
Van Eck
Miranda
M
Divison of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands. m.eck@LACDR.LeidenUniv.nl
Hoekstra
Menno
M
Out
Ruud
R
Bos
I Sophie T
IS
Kruijt
J Kar
JK
Hildebrand
Reeni B
RB
Van Berkel
Theo J C
TJ
D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000172:deficiency / Q000378:metabolism*
D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B