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Originally published In Press as doi:10.1074/jbc.M402631200 on May 6, 2004

J. Biol. Chem., Vol. 279, Issue 28, 29195-29201, July 9, 2004
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Oleic Acid Modulates the Post-translational Glycosylation of Macrophage ApoE to Increase Its Secretion*

Zhi Hua Huang, DeSheng Gu, and Theodore Mazzone{ddagger}

From the Departments of Medicine and Pharmacology, Section of Diabetes and Metabolism, University of Illinois at Chicago, Chicago, Illinois 60612

There has been increasing interest in a potential role for fatty acids in adversely affecting organismal substrate utilization and contributing to the cardiovascular complications in insulin resistance. Fatty acids have already been implicated in regulating the expression of a number of genes in resident cells of the vessel wall. In the current studies, we evaluated a potential role for fatty acids in the regulation of macrophage apoE expression. Incubation in oleic acid increased the synthesis and secretion of apoE by human monocyte-derived macrophages. Part of this stimulation was mediated at a post-translational locus. Oleic acid increased the secretion of apoE from macrophages that constitutively expressed a human apoE3 cDNA. Incubation in palmitic acid decreased apoE secretion from these cells. The effect of oleic acid on apoE secretion could not be accounted for by the known effect of fatty acid on cellular sterol, because incubation in oleic acid did not suppress the degradation of nascent apoE. Incubation in oleic acid for at least 6 h was required to observe an effect on apoE secretion. Oleic acid altered the glycosylation pattern of cellular and secreted apoE, with a loss of the most heavily sialylated isoform. Oleic acid had no effect on the glycosylation of interleukin 6 secreted from macrophages. Elimination of apoE glycosylation, by substitution of threonine 194 with alanine, eliminated oleic acid-mediated stimulation of apoE secretion. These results indicate that oleic acid increases apoE secretion from macrophages at a locus involving post-translational glycosylation.


Received for publication, March 8, 2004 , and in revised form, April 30, 2004.

* This work was supported by Grant HL 39653 from the National Institutes of Health (to T. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: Dept. of Medicine and Pharmacology, Section of Diabetes and Metabolism, M/C 797, University of Illinois, 1819 W. Polk St., Chicago, IL 60612. Tel.: 312-996-7989; Fax: 312-413-0437; E-mail: tmazzone{at}uic.edu.


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