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Originally published In Press as doi:10.1194/jlr.M700024-JLR200 on March 5, 2007

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Journal of Lipid Research, Vol. 48, 1353-1361, June 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification

Marit Westerterp1,*,{dagger}, Jimmy F. P. Berbée*,{dagger}, Dianne J. M. Delsing*, Miek C. Jong*, Marion J. J. Gijbels*,§, Vivian E. H. Dahlmans*, Erik H. Offerman*, Johannes A. Romijn{dagger}, Louis M. Havekes*,{dagger},** and Patrick C. N. Rensen*,{dagger}

* Netherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, Leiden, The Netherlands
{dagger} Department of General Internal Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
** Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
§ Departments of Molecular Genetics and Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

Published, JLR Papers in Press, March 5, 2007.

1 To whom correspondence should be addressed. e-mail: m.westerterp{at}lumc.nl

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-I-deficient 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.

Supplementary key words lipoprotein • macrophage • skin • lipoprotein lipase • triglyceride

Abbreviations: acat1–/–, acyl-CoA:cholesterol acyltransferase 1-deficient; apoC-I, apolipoprotein C-I; APOC1+/+, homozygous human apoC-I transgenic; APOC1+/0, hemizygous human apoC-I transgenic; apoc1–/–, apoC-I-deficient; BMIPP, 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid; CE, cholesteryl ester; dgat1–/–, acyl-CoA:diacylglycerol acyltransferase 1-deficient; FAR, fatty acyl-CoA reductase; FPLC, fast-performance liquid chromatography; GAG, glycosaminoglycan; lpl–/–, LPL-deficient; LPS, lipopolysaccharide; scd1–/–, stearoyl-CoA desaturase 1-deficient; TG, triglyceride


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