Insulin resistance and increased IGF-1, disruption of the adipokine equilibrium with increased leptin, interleukins, and TNF-α and decreased adiponectin, augmented peripheral aromatization and production of estrogens, tissue hypoxia and locally disrupted inflammation, and a pivotal role of mesenchymal adipose tissue cells seem to be core motifs in the pathogenesis of obesity-related gynecologic cancers. The gene discussed is LEP; the disease is Insulin resistance.