Consistent with this notion, the pathophysiology of obesity is characterized not only by the increased expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α but also by the higher expression of PEDF and long-term obesity may inhibit regulatory responses resulting in a systemic pro-inflammatory state. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.