Specifically, setmelanotide was found to be effective by inducing biased signalling of the MC4R and thereby reducing feelings of hunger and leading to substantial weight loss in patients with POMC or leptin receptor deficiency.
Proopiomelanocortin (POMC) and its derived peptides, in particular alpha-MSH, have been shown to play a crucial role in the regulation of hunger, satiety and energy homeostasis.
We suggest that beta-MSH rather than alpha-MSH is the key ligand at the MC4-R populations that regulate feeding, and that inhibition of tonic release of beta-MSH is one mechanism contributing to hunger in under-feeding.