Thus, obesity is associated with selective insulin and leptin resistance at the level of the CNS, whereby leptin and insulin action are attenuated in certain neuronal populations while others become more leptin- and insulin-sensitive, thus further promoting hyperphagia, weight gain and a dysregulation in glucose homeostasis (Könner and Brüning, 2012). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.