Adipogenic differentiating agents regulate expression of fatty acid binding protein and CD36 in the J744 macrophage cell line.
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 of macrophage aP2 and CD36, a fatty acid membrane binding protein and scavenger receptor, in response to the 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 the expression of PPARgamma and C/EBPalpha in macrophages. Our data demonstrate 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.
Sun
Li
L
Center of Vascular Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Nicholson
Andrew C
AC
Hajjar
David P
DP
Gotto
Antonio M
AM
Han
Jihong
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D022762:CCAAT-Enhancer-Binding Proteins; D018955:CD36 Antigens; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D012333:RNA, Messenger; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine