In obesity, cytokines secreted by immune cells and adipocytes such as tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) or IL-6, are increased and induce IR through multiple mechanisms, including activation of serine/threonine kinases, reduction of IRS1, GLUT4 and PPAR-γ expression or activation of suppressor of cytokine signalling 3 in adipocytes3,23,.27 The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.