Numerous hypotheses have been proposed to account for the unfavorable prognostic implications of obesity, including concentrations of circulating hormones such as estrogen and androgens, reduced levels of sex hormone-binding globulin which elevate free estradiol and free testosterone, elevated levels of insulin and insulin-like growth factor, diminished levels of insulin-like growth factor binding protein, elevated levels of cortisol and leptin, augmented levels of cytokines, disrupted lipid metabolism, and heightened levels of inflammation culminating in compromised immune function.20 This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.