NPFFR2 and obesity due to melanocortin 4 receptor deficiency: Our results show that NPFFR2 signalling in the arcuate nucleus of the hypothalamus is crucial in maintaining a basal tone of neuropeptide Y (NPY), lack of which renders downstream pathways that control adaptive thermogenesis in the BAT unresponsive to caloric excess and consequently leads to exacerbated diet-induced obesity.