Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment.
The melanocortin-4 receptor (MC4R) - embedded in the leptin-melanocortin pathway - is activated by proopiomelanocortin (POMC)-derived neuropeptides such as α- and β-melanocyte-stimulating hormone (MSH) and plays an important role in hypothalamic body-weight regulation. Accordingly, MC4R is a potential drug target to combat obesity. Previous attempts to develop MC4R agonists failed due to ineffectiveness or severe adverse events. Recently, a new generation of MC4R ligands was developed. 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. This new potential pharmacological treatment option could be beneficial for further groups of obese patients with defects in the leptin-melanocortin signalling pathway.
['Kühnen|Peter|P|', 'Krude|Heiko|H|', 'Biebermann|Heike|H|']
D000818:Animals D019440:Anti-Obesity Agents D000076722:Drug Development D006801:Humans D058990:Molecular Targeted Therapy D009765:Obesity D044105:Receptor, Melanocortin, Type 4 D015398:Signal Transduction
signalling obesity treatment MC4R mutation