The recent approval of Setmelanotide, an MC4R agonist, for treating obesity caused by deficiencies in proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or Leptin Receptor (Markham, 2021), has heightened scientific interest in the effects of MCRs on feeding and energy balance (Table 1). This evidence concerns the gene POMC and obesity due to melanocortin 4 receptor deficiency.