INS and obesity due to melanocortin 4 receptor deficiency: Previous reports indicate that brain inactivation of the melanocortin-4 receptor (MC4R) subtype promotes hyperphagia, obesity, and a T2D phenotype, attenuates preclinical 5-HT2CR agonist's anorectic and glycemic effects, and that MC4Rs specifically within cholinergic neurons play a physiological role in the regulation of hepatic insulin sensitivity [11], [24], [25].