TNFα impairs insulin signaling in adipocytes and hepatocytes through activation of stress-related protein kinases, as JNK-1, and activation of the IKKB/NF-κB pathway (Hirosumi et al., 2002; Arkan et al., 2005; Tarantino and Caputi, 2011) In addition, TNFα stimulates inhibitory phosphorylation of the serine residues of IRS-1, which is recognized as the major pathway in IR, corroborating the link between inflammation, obesity and IR (Wellen and Hotamisligil, 2005). The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.