Title
Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism
Author
TNO Preventie en Gezondheid
Out, R.
Kruijt, J.K.
Rensen, P.C.N.
Hildebrand, R.B.
de Vos, P.
van Eck, M.
van Berkel, T.J.C.
Publication year
2004
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
Subject
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
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DOI
https://doi.org/10.1074/jbc.m401170200
TNO identifier
237718
ISSN
0021-9258
Source
Journal of Biological Chemistry, 279 (279), 18401-18406
Document type
article