Document Detail


Visfatin is induced by peroxisome proliferator-activated receptor gamma in human macrophages.
MedLine Citation:
PMID:  20608974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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(+).
Authors:
Thérèse Hèrvée Mayi; Christian Duhem; Corinne Copin; Mohamed Amine Bouhlel; Elena Rigamonti; François Pattou; Bart Staels; Giulia Chinetti-Gbaguidi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-01
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-12     Completed Date:  2010-09-08     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  3308-20     Citation Subset:  IM    
Affiliation:
University Lille Nord de France, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blotting, Western
Cells, Cultured
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation, Enzymologic* / drug effects
Humans
Leukocytes, Mononuclear / enzymology*
Mice
Mice, Inbred C57BL
Molecular Sequence Data
NAD / chemistry
Nicotinamide Phosphoribosyltransferase / genetics,  metabolism*
PPAR gamma / agonists,  metabolism*
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/PPAR gamma; 0/RNA, Messenger; 53-84-9/NAD; EC 2.4.2.12/Nicotinamide Phosphoribosyltransferase
Comments/Corrections

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