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Visfatin is induced by peroxisome proliferator‐activated receptor gamma in human macrophages
Author(s) -
Mayi Thérèse Hèrvée,
Duhem Christian,
Copin Corinne,
Bouhlel Mohamed Amine,
Rigamonti Elena,
Pattou François,
Staels Bart,
ChinettiGbaguidi Giulia
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07729.x
Subject(s) - adipose tissue macrophages , adipose tissue , adipocyte , macrophage , endocrinology , medicine , peroxisome proliferator activated receptor , receptor , chemistry , biology , white adipose tissue , microbiology and biotechnology , in vitro , biochemistry
Obesity is a low‐grade chronic inflammatory disease associated with an increased number of macrophages (adipose tissue macrophages) in adipose tissue. Within the adipose tissue, adipose tissue macrophages are the major source of visfatin/pre‐B‐cell colony‐enhancing factor/nicotinamide phosphoribosyl transferase. The nuclear receptor peroxisome proliferator‐activated receptor gamma (PPARγ) 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 (bone marrow‐derived macrophage) and human (primary human resting macrophage, classical macrophage, alternative macrophage or adipose tissue macrophage) macrophage models and pre‐adipocyte‐derived adipocytes. We show that synthetic PPARγ ligands increase visfatin gene expression in a PPARγ‐dependent manner in primary human resting macrophages and in adipose tissue macrophages, but not in adipocytes. The threefold increase of visfatin mRNA was paralleled by an increase of protein expression (30%) and secretion (30%). Electrophoretic mobility shift assay 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 that this regulation is dampened in the presence of visfatin small interfering RNA or by the visfatin‐specific inhibitor FK866. Taken together, our results suggest that PPARγ regulates the expression of visfatin in macrophages, leading to increased levels of NAD + .