Therefore, obesity is thought to lead to decreases not only in plasma adiponectin levels but also in AdipoR1/R2 expression, thereby reducing adiponectin sensitivity and inducing insulin resistance, which, in turn, leads to hyperinsulinemia thus resulting in a “vicious cycle” (53) (Figure 1). The gene discussed is ADIPOQ; the disease is obesity due to melanocortin 4 receptor deficiency.