However, obesity can also increase bone reabsorption through the increased release of pro-inflammatory cytokines (Figure 1), such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), which stimulate the formation and activity of osteoclasts through the receptor activator of the nuclear factor bappa-beta ligand (RANKL)/(RANK)/Osteoprotegerin (OPG) pathway [133,134,135]. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.