Unsaturated Fatty Acids Repress the Expression of Adipose Fatty Acid Binding Protein (aP2) in RAW 264.7 Macrophages

Abstract

Adipocyte fatty acid binding protein, aP2, present in macrophages has been implicated in the integration of lipid metabolism and inflammatory response, contributing to development of insulin resistance and atherosclerosis. We investigated the modulation of aP2 expression by inflammatory insults and fatty acids in RAW 264.7 macrophages. When the cells were incubated with lipopolysaccharides (LPS; 100 ng/ml) or 10 ng/ml of tumor necrosis factor α for 18 h, aP2 mRNA and protein levels were drastically increased. Unsaturated fatty acids (100 μM of 18:1, 18:2, 18:3, 20:5 in complex with BSA), but not saturated fatty acids (16:0), significantly repressed the basal aP2 expression and abolished induction of aP2 expression by LPS. Trichstatin A (TSA), a histone deacetylase (HDAC) inhibitor, increased aP2 mRNA levels but abolish the repressive effect of 18:2 on aP2 expression in unstimulated and LPS‐stimulated macrophages. Depletion of HDAC3 or c‐Jun by siRNA significantly increased aP2 expression in unstimulated macrophages. In summary, our data suggest that basal aP2 expression in macrophages is likely to be repressed by c‐Jun in association with a corepressor complex containing HDAC3 and unsaturated fatty acids may inhibit the basal as well as LPS‐induced aP2 expression by modulating the recruitment or activity of co‐repressor complex to the promoter of aP2.Grant Funding Source: Faculty Seed Grant from University of Nebraska‐Lincoln Research Council