The roles of obesity and metabolic disturbance in cancer etiopathogenesis comprise34 the following: (1) hyperinsulinemia/insulin resistance and abnormalities of the insulin-like growth factor-I (IGF-I) system and signaling; (2) alterations in adipocytokine pathophysiology; (3) an altered intestinal microbiome; and (4) microenvironment and cellular perturbations. Here, IGF1 is linked to obesity due to melanocortin 4 receptor deficiency.