TNF and obesity due to melanocortin 4 receptor deficiency: It has been demonstrated that obesity (34), T2D (9,16,35) and PCOS (3,8) are associated with a state of chronic low-grade inflammation, mediated by release of several inflammatory mediators from adipocytes and immune cells - such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1 - which have been involved in the development of IR and inflammatory response during periodontal disease (34,36).