Title
Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification
Author
TNO Kwaliteit van Leven
Westerterp, M.
Berbée, J.F.P.
Delsing, D.J.M.
Jong, M.C.
Gijbels, M.J.J.
Dahlmans, V.E.H.
Offerman, E.H.
Romijn, J.A.
Havekes, L.M.
Rensen, P.C.N.
Publication year
2007
Abstract
Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In this study, we tested the hypothesis that apoC-I interferes with cellular FFA uptake independent of LPL activity. The cutaneous abnormalities of APOC1+/+ mice were not affected after transplantation to wild-type mice, indicating that locally produced apoC-I prevents lipid entry into the skin. Subsequent in vitro studies with apoC-Ideficient versus wild-type macrophages revealed that apoC-I reduced the cell association and subsequent esterification of [3H]oleic acid by ∼35% (P < 0.05). We speculated that apoC-I binds FFA extracellularly, thereby preventing cell association of FFA. We showed that apoC-I was indeed able to mediate the binding of oleic acid to otherwise protein-free VLDL-like emulsion particles involving electrostatic interaction. We conclude that apoC-I binds FFA in the circulation, thereby reducing the availability of FFA for uptake by cells. This mechanism can serve as an additional mechanism behind the resistance to obesity and the cutaneous abnormalities of APOC1+/+ mice. Copyright ©2007 by the American Society for Biochemistry and Molecular Biology, Inc.
Subject
Biomedical Research
Lipoprotein
Lipoprotein lipase
Skin
Triglyceride
very low density lipoprotein
animal cell
animal experiment
animal tissue
controlled study
electricity
esterification
female
in vitro study
mouse
nonhuman
phenotype
skin transplantation
wild type
Animals
Apolipoprotein C-I
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Esterification
Fatty Acids, Nonesterified
Female
Humans
Lipoproteins, VLDL
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Oleic Acid
Phenotype
Protein Binding
Skin
Skin Abnormalities
Skin Transplantation
To reference this document use:
http://resolver.tudelft.nl/uuid:da7887ab-328d-49d1-915e-7118aaced47f
DOI
https://doi.org/10.1194/jlr.m700024-jlr200
TNO identifier
240022
ISSN
0022-2275
Source
Journal of Lipid Research, 48 (48), 1353-1361
Document type
article