Autophagy is rapidly induced by nutrient deprivation (fasting) and evidence is accumulating that this fasting-induced autophagy is defective regulated in insulin sensitive tissues such as liver, muscle, and adipose, in the context of obesity, which underpins an unprecedented role of autophagy in the manifestation of obesity-induced metabolic derangement [22,23]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.