INS and obesity due to melanocortin 4 receptor deficiency: As summarized by Ortega and collages [82], obesity increases chronic inflammation and cytokine production, which affects insulin-dependent tissues and beta cells; peripheral tissues are impaired by the lipotoxicity exerted by ectopic lipid stores in obese subjects, and the increased secretion of a set of autocrine and paracrine products by adiponectin downregulation finally produces the loss of insulin sensitivity concomitant with impaired insulin production in type-2 diabetic patients.