The decreased cell surface insulin receptor number in people with obesity is thought to be at least in part due to the obesity-associated increase in insulin secretion and concomitant chronic hyperinsulinemia, because receptor number is inversely related to plasma insulin concentration and lowering insulin by administering diazoxide or fasting increased the number of receptors [119,126,127,128,129]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.