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 (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 (PPARgamma) exerts anti-inflammatory effects in macrophages by inhibiting cytokine production and enhancing alternative differentiation. In this study, we investigated whether PPARgamma 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 PPARgamma ligands increase visfatin gene expression in a PPARgamma-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 PPARgamma induces visfatin promoter activity in human macrophages by binding to a DR1-PPARgamma response element. Finally, we show that PPARgamma 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 PPARgamma regulates the expression of visfatin in macrophages, leading to increased levels of NAD(+).
Mayi
Thérèse Hèrvée
TH
University Lille Nord de France, France.
Duhem
Christian
C
Copin
Corinne
C
Bouhlel
Mohamed Amine
MA
Rigamonti
Elena
E
Pattou
François
F
Staels
Bart
B
Chinetti-Gbaguidi
Giulia
G
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D004791:Enzyme Inhibitors; D047495:PPAR gamma; D012333:RNA, Messenger; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase