Peroxisome proliferator-activated receptor γ agonists inhibit adipocyte expression of α1-acid glycoprotein

alpha 1-Acid glycoprotein (alpha 1-AGP) is an acute phase protein that can potentiate cytokine secretion by mononuclear cells and may induce thrombosis by stabilizing the inhibitory activity of plasminogen activator inhibitor-1. Thus, alpha 1-AGP may promote pathobiologies associated with type 2 diabetes mellitus (T2DM) including insulin resistance and cardiovascular disease. Here, we demonstrate that antidiabetic peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists inhibited expression of 3T3-L1 adipocyte alpha 1-AGP in a concentration- and time-dependent manner via an apparent PPAR gamma-mediated mechanism. As a result, synthesis and secretion of the glycoprotein was reduced. While PPAR gamma agonist regulation of genes with functional peroxisome proliferator response elements in their promoter such as phosphoenolpyruyate carboxykinase were unaffected when cellular protein synthesis was inhibited, downregulation of alpha 1-AGP mRNA was ablated thereby supporting the proposition that PPAR gamma activation inhibits alpha 1-AGP expression indirectly. These results suggest a potential novel adipocytic mechanism by which PPAR gamma agonists may ameliorate T2DM-associated insulin resistance and cardiovascular disease. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.