Melanocortin 4 Receptor Pathway Dysfunction in Obesity: Patient Stratification Aimed at MC4R Agonist Treatment

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

OBJECTIVE 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...

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Association between the Melanocortin-4 Receptor (MC4R) Gene Polymorphisms and Growth Trait in Sumba Ongole Cattle

Melanocortin-4 receptor (MC4R) gene has been known as a candidate gene for growth traits in livestock. This research was aimed to identify the polymorphism of MC4R gene and its association with growth traits in Sumba Ongole (SO) cattle. The growth traits data consist of body weight and body size. Eighty four blood samples were collected and used for DNA isolation. The...

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Anti-melanocortin-4 receptor autoantibodies in obesity.

BACKGROUND The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. METHODS The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluate...

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Melanocortin-4 receptor agonists for the treatment of obesity.

The identification of a highly efficacious anti-obesity agent remains an illusive goal. While many avenues of investigation have been pursued, none of the existing compounds claim much more than a 10% reduction in weight in humans (over a one year period with diet and exercise). Nonetheless, the potential reward for fulfilling this unmet medical need has kept interest levels high in the researc...

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A Novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity.

The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled receptor superfamily and signals through the activation of adenylyl cyclase. The MC4R mutations are the most common known monogenic cause of human obesity. However, no such mutations have been found in Japanese obese subjects. Here we report a novel homozygous missense mutation of MC4R (G98R) in a no...

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ژورنال

عنوان ژورنال: The Journal of Clinical Endocrinology & Metabolism

سال: 2018

ISSN: 0021-972X,1945-7197

DOI: 10.1210/jc.2018-00258