Depletion of leptin or insulin, or their receptors, generally results in increased food intake and obesity mediated by the brain, largely arising from lowered sensitivity to meal-generated satiety signals [19,21,22]; type 1 diabetes represents a pathological state of insulin depletion leading to weight loss due to severely impaired glucose utilization and reduced ability of adipocytes to store fat. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.