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).