LEP and obesity due to melanocortin 4 receptor deficiency: Studies in mouse models of obesity, including leptin-deficient (OB) and leptin-receptor-deficient (DB) genetically obese models as well as the high-fat diet-induced-obese (DIO) model (Table 1) have identified several immunological mechanisms for the increased pathogenesis and mortality that mirrors what has been seen in humans (26–29).