regulated by LPL activity and involves proteoglycans and SR-BI

LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipo- protein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL re- ceptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance irrespective of these receptors and to determine the mechanisms involved in the hepatic remnant uptake. Ad- ministration of an adenovirus expressing LPL (AdLPL) into lrp 2 ldlr 2/2 vldlr 2/2 mice reduced both VLDL-triglyceride (TG) and VLDL-total cholesterol (TC) levels. Conversely, in- hibition of LPL by AdAPOC1 increased plasma VLDL-TG and VLDL-TC levels. Metabolic studies with radiolabeled VLDL-like emulsion particles showed that the clearance and hepatic association of their remnants positively corre- lated with LPL activity. This hepatic association was inde- pendent of the bridging function of LPL and HL, since heparin did not reduce the liver association. In vitro studies demonstrated that VLDL-like emulsion particles avidly bound to the cell surface of primary hepatocytes from lrp 2 ldlr 2/2 vldlr 2/2 mice, followed by slow internalization, and involved heparin-releaseable cell surface proteins as well as scavenger receptor class B type I (SR-BI). Collec- tively, we conclude that hepatic VLDL remnant uptake in the absence of the three classical apoE-recognizing recep- tors is regulated by LPL activity and involves heparan sulfate proteoglycans and SR-BI.—Hu, L., 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. Willems van Dijk, and P. C. N. Rensen. The hepatic uptake of VLDL in lrp 2 ldlr 2/2 vldlr 2/2 mice is regulated by LPL activity and involves proteoglycans and SR-BI. J. Lipid Res. 2008. 49: 1553-1561.