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Molecular Physiology & Biophysics

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.

AUTHORS

Collet TH , Dubern B , Mokrosinski J , Connors H , Keogh JM , Mendes de Oliveira E , Henning E , Poitou-Bernert C , Oppert JM , Tounian P , Marchelli F , Alili R , Le Beyec J , Pépin D , Lacorte JM , Gottesdiener A , Bounds R , Sharma S , Folster C , Henderson B , O'Rahilly S , Stoner E , Gottesdiener K , Panaro BL , Cone RD , Clément K , Farooqi IS , Van der Ploeg LHT , . Molecular metabolism. 2017 10 ; 6(10). 1321-1329

ABSTRACT

Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency.

Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency.

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