Univ Lille Nord de France, F-59000 Lille, France.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):458-62. doi: 10.1016/j.bbrc.2010.12.002. Epub 2010 Dec 8.
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.
脂肪组织巨噬细胞（ATM）是内脏脂肪脂肪因子 visfatin 的主要来源，其在肥胖期间上调。visfatin 也被认为在 B 细胞分化（前 B 细胞集落增强因子（PBEF））和 NAD 生物合成（烟酰胺磷酸核糖转移酶（NAMPT））中发挥作用，其被认为在炎症中发挥作用。肝 X 受体（LXR）和过氧化物酶体增殖物激活受体（PPAR）γ是在巨噬细胞中表达的核受体，可控制炎症反应。最近，我们报道了 visfatin 是人类巨噬细胞中 PPARγ 的靶基因。在这项研究中，我们检查了 LXR 是否调节巨噬细胞 visfatin 的表达。合成 LXR 配体以依赖于 LXR 的方式降低人源和鼠源巨噬细胞中 visfatin 基因的表达。mRNA 的减少伴随着蛋白分泌的减少。因此，观察到 NAD（+）浓度的适度和短暂下降。有趣的是，LXR 的激活降低了人源巨噬细胞中 PPARγ 诱导的 visfatin 基因和蛋白分泌。我们的结果表明，在人类巨噬细胞中，visfatin 是由 LXR 和 PPARγ 途径相反调节的基因。
