Such modifications then activate NF-κB that is involved in the expression of proinflammatory mediators such as TNF and IL-6,343,344 and that induces key steroidogenic molecules, like CYP11A1, CYP17A1 and StAR, leading to further aggravation of hyperandrogenemia.345–347 Altogether, obesity and IR play pivotal role in women with PCOS and subsequent metabolic complications, and targeting these areas may become an important therapeutic approach for effectively reducing incidence of this pathology. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.