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Introduction
White adipose tissue (WAT) was, until recently, only regarded as a predominant site of energy storage with important roles in the control of energy homeostasis. However, WAT is now considered to be a predominant endocrine organ in humans, secreting a wide range of biologically active molecules, including numerous adipokines (1). A number of these adipokines, which are predominantly produced by WAT, exhibit the ability to modulate metabolic and inflammatory processes and are hypothesized to contribute to the pathophysiology of obesity-linked diseases (2). In particular, articular adipose tissue (AAT) is highly reactive, secreting considerable quantities of pro-inflammatory and anti-inflammatory cytokines and classical adipokines when stimulated (3). Thus, all the predominant adipose-derived products, termed adipokines, participate in inflammation and immunity. These include leptin, adiponectin, visfatin and resistin.
Adipokine levels are elevated in the sera and synovial fluids of patients with rheumatoid arthritis (RA). This suggests that adipokines are involved in the pathogenesis of RA by exerting potent modulatory effects on target tissues and cells involved in rheumatic disease, including cartilage, synovium, bone, and various immune cells (4,5). Adiponectin also induces the in vitro production of pro-inflammatory cytokines, including interleukin (IL)-6, matrix metalloproteinase (MMP)-1 and IL-8 from RA synovial fibroblasts (6,7). Thus, adiponectin is hypothesized to exert significant pro-inflammatory and matrix-degrading effects. Leptin stimulates T cell-mediated immunity, cytokine release from monocytes/macrophages and the differentiation of hematopoietic cells (8). Visfatin is a novel mediator of innate immunity. It is key in the persistence of inflammation through its capacity to inhibit neutrophil apoptosis (9). Furthermore, visfatin activates transcription factors, including nuclear factor (NF)-κB and activator protein (AP)-1 and induces the production of IL-6, IL-8, MMP-1 and MMP-3 in RA synovial fibroblasts and IL-6 and tumor necrosis factor (TNF) in monocytes (10). Human resistin also has pro-inflammatory functions, including the activation of NF-κB-dependent pathways to produce TNF-α, IL-6 and IL-1β in human peripheral blood mononuclear cells (11). It is widely accepted, that adipokines are important in the pathogenesis of RA, yet the in vivo role of adipokines and their association with disease activity is poorly understood. Additional insight into the role of adipokines may aid in the development of novel therapeutic agents. In this study, the modulation of serum adipokines (adiponectin, leptin, resistin and visfatin) was evaluated depending on...