Visfatin is induced by peroxisome proliferator-activated receptor gamma in human macrophages.

Obesity is a low grade chronic inflammatory disease associated with an increased number of macrophages (ATM) in adipose tissue. Within the adipose tissue, ATM are the major source of visfatin/PBEF/NAMPT. The nuclear receptor Peroxisome Proliferator-Activated Receptor (PPAR)γ exerts anti-inflammatory effects in macrophages by inhibiting cytokine production and enhancing alternative differentiation. In this study, we investigated whether PPARγ modulates visfatin expression in murine (BMDM) and human (RM, M1, M2, ATM) macrophage models and preadipocyte-derived adipocytes. We show that synthetic PPARγ ligands increased visfatin gene expression in a PPARγ-dependent manner in primary human macrophages (RM) and ATM, but not in adipocytes. The increase of visfatin mRNA (3-fold) was paralleled by an increase of protein expression (30%) and secretion (30%). Electrophoretic Mobility Shift Assay (EMSA) experiments and transient transfection assays indicated that PPARγ induces visfatin promoter activity in human macrophages by binding to a DR1-PPARγ response element. Finally, we show that PPARγ ligands increase NAD+ production in primary human macrophages and this regulation is dampened in the presence of visfatin siRNA or by the visfatin-specific inhibitor FK866. Taken together, our results suggest that PPARγ regulates the expression of visfatin in macrophages leading to increased NAD+ levels.