title: Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages.
abstract: Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation. Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR)γ are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPARγ target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD(+) concentration was observed. Interestingly, LXR activation decreased the PPARγ-induced visfatin gene and protein secretion in human macrophages. Our results identify visfatin as a gene oppositely regulated by the LXR and PPARγ pathways in human macrophages.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France.
authors.forename: Thérèse Hèrvée
authors.initials: TH
authors.lastname: Mayi
authors.forename: Elena
authors.initials: E
authors.lastname: Rigamonti
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000071518:Liver X Receptors; D008264:Macrophages / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D016207:Cytokines; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human