J. Lipid Res.
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A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print July 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300084-JLR200
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Submitted on February 19, 2003
Revised on July 7, 2003
Accepted on July 7, 2003

Adipogenic differentiating agents regulate expression of fatty acid binding protein (aP2) and CD36 in the J774 macrophage cell line

Li Sun, Andrew C. Nicholson, David P. Hajjar, Antonio M. Gotto Jr, and Jihong Han

Center of Vascular Biology, Weill Medical College of Cornell University, New York, NY 10021

Corresponding Author: jhan{at}med.cornell.edu

Adipocyte fatty acid binding protein (aP2) is a key mediator of intracellular transport and metabolism of fatty acids. Its expression during adipocyte differentiation is regulated through the actions of peroxisome proliferator-activated receptor-gamma (PPARgamma ) and CCAAT/enhancer binding protein-alpha (C/EBPalpha ). Macrophages also express aP2 and the lack of macrophage aP2 significantly reduces atherosclerotic lesion size in hypercholesterolemic mice. We investigated the regulation of expression macrophage aP2 and CD36, a fatty acid membrane binding protein and scavenger receptor, in response to adipogenic agents, isobutylmethylxanthine (IBMX), insulin, and dexamethasone, a combination of agents shown to induce fibroblast to adipocyte differentiation. Treatment of J774 macrophages with adipogenic agents significantly induced aP2 mRNA expression while CD36 expression was inhibited. Dexamethasone was essential and sufficient to induce aP2 expression and insulin had a synergistic effect. However, IBMX antagonized induced-aP2 expression. aP2 protein expression and 14C-oleic acid uptake by macrophages were also increased by dexamethasone. Unlike what occurs in adipocytes, adipogenic agents had mixed effects on expression of PPARgamma or C/EBPalpha in macrophages. Our data demonstrated differences in the regulation of aP2 in adipocytes and macrophages and show that macrophage aP2 expression by adipogenic agents is independent of the PPARgamma and/or C/EBPalpha signaling pathway


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