Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties

Abstract

Adipocytokines are mainly adipocyte-derived cytokines regulating metabolism and as such are key regulators of insulin resistance. Some adipocytokines such as adiponectin and leptin affect immune and inflammatory functions. Visfatin (pre-B cell colony-enhancing factor) has recently been identified as a new adipocytokine affecting insulin resistance by binding to the insulin receptor. In this study, we show that recombinant visfatin activates human leukocytes and induces cytokine production. In CD14+ monocytes, visfatin induces the production of IL-1β, TNF-α, and especially IL-6. Moreover, it increases the surface expression of costimulatory molecules CD54, CD40, and CD80. Visfatin-stimulated monocytes show augmented FITC-dextran uptake and an enhanced capacity to induce alloproliferative responses in human lymphocytes. Visfatin-induced effects involve p38 as well as MEK1 pathways as determined by inhibition with MAPK inhibitors and we observed activation of NF-κB. In vivo, visfatin induces circulating IL-6 in BALB/c mice. In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn’s and ulcerative colitis patients compared with healthy controls. Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy. Visfatin can be considered a new proinflammatory adipocytokine.

Involvement of visfatin in palmitate-induced upregulation of inflammatory cytokines in hepatocytes

“…When administered to mice, visfatin had similar effects on proinflammatory cytokine levels, especially increasing circulating IL-6 [18,19]. Furthermore, Li et al [20] demonstrated that visfatin affects macrophage function and IL-6 production.…”

“…A number of reports concerning the proinflammatory effects of visfatin have shown that it dose-dependently upregulates the production of IL-1α, IL-6, and TNF-α in human monocytes [18,19]. When administered to mice, visfatin had similar effects on proinflammatory cytokine levels, especially increasing circulating IL-6 [18,19].…”

Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

“…Since eNAMPT has been implicated in the regulation of inflammatory responses [15,[41][42][43], and since MPN-associated myelofibrosis has been interpreted as an inflammatory disease with uncontrolled myeloproliferation and cytokine secretion [7], we investigated the additional role of eNAMPT as an inflammatory cytokine. For this endeavor, we correlated eNAMPT levels to the marker of general inflammation, that is, plasma level of hs-CRP.…”

Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis

“…From an intracellular standpoint, visfatin is a dimeric type II phosphoribosyltransferase that serves a critical role as the rate-limiting step in the biosynthesis of NAD from nicotinomide and regulates the activity of NAD-dependent deacetylase Sirt1 in mammalian cells (30). On the other hand, visfatin appears to play an important role as a cytokine, secreted extracellularly in response to inflammatory stimuli such as lipopolysaccharide, TNF-␣, IL-1␤, and IL-6, capable of modulating the innate immune response in states of systemic inflammation and sepsis (6,15). Indeed, elegant experiments by Jia and colleagues (6), clearly demonstrate that visfatin is upregulated in neutrophils and macrophages, by proinflammatory stimuli of both host and microbial origin, and that it plays an essential role in inhibiting neutrophil apoptosis.…”