Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Author: Out, R. · Kruijt, J.K. · Rensen, P.C.N. · Hildebrand, R.B. · Vos, P. de · Eck, M. van · Berkel, T.J.C. van
Type:article
Date:2004
Institution: TNO Preventie en Gezondheid
Source:Journal of Biological Chemistry, 18, 279, 18401-18406
Identifier: 237718
doi: doi:10.1074/jbc.M401170200
Keywords: Biology · Biomedical Research · Emulsions · Metabolism · Proteins · Cell association · High density lipoproteins (HDL) · Biochemistry · Chylomicron · High density lipoprotein cholesterol · Low density lipoprotein receptor · Low density lipoprotein receptor related protein · Oxidized low density lipoprotein · Scavenger receptor · Scavenger receptor BI · Triacylglycerol · Unclassified drug · Animal cell · Animal experiment · Cholesterol transport · Controlled study · Emulsion · Internalization · Lipid metabolism · Liver cell · Molecular recognition · Mouse · Nonhuman · Postprandial state · Animals · Antigens, CD36 · Binding Sites · Biological Transport · Chylomicron Remnants · Chylomicrons · Emulsions · Hepatocytes · Mice · Mice, Mutant Strains · Receptors, Immunologic · Receptors, Scavenger · Scavenger Receptors, Class B · Tissue Distribution · Triglycerides · Animalia

Abstract

The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160 nm-sized triglyceride-rich chylomicron-like emulsion particles to freshly isolated hepatocytes from SR-BI-deficient mice is greatly reduced (>70%), as compared with wild-type littermate mice. Competition experiments show that the association of emulsion particles with isolated hepatocytes is efficiently competed for (>70%) by the well established SR-BI ligands, HDL and oxidized low density lipoprotein (LDL), whereas LDL is ineffective. Upon injection into SR-BI-deficient mice the hepatic association of emulsion particles is markedly decreased (∼80%) as compared with wild-type mice. The relevance of these findings for in vivo chylomicron (remnant) metabolism was further evaluated by studying the effect of SR-BI deficiency on the intragastric fat load-induced postprandial triglyceride response. The postprandial triglyceride response is 2-fold higher in SR-BI-deficient mice as compared with wild-type littermates (area-under-the-curve 39.6 ± 1.2 versus 21.1 ± 3.6; p < 0.005), with a 4-fold increased accumulation of chylomicron (remnant)-associated triglycerides in plasma at 6 h after intragastric fat load. We conclude that SR-BI is important in facilitating chylomicron (remnant) metabolism and might function as an initial recognition site for chylomicron remnants whereby the subsequent internalization can be exerted by additional receptor systems like the LDL receptor and LDL receptor-related protein. Chemicals / CAS: Antigens, CD36; Chylomicron Remnants; Chylomicrons; Emulsions; Receptors, Immunologic; Receptors, Scavenger; Scavenger Receptors, Class B; Triglycerides