What it means
When fat stores are adequate, the hormone leptin triggers nerve cells to make a signal that activates MC4R. That signal reduces hunger and supports energy use. This is called the leptin-melanocortin pathway.
If any step fails, hunger can be intense and constant from early childhood. Rare defects in POMC, PCSK1 or the leptin receptor break the pathway upstream of MC4R. Variants in the MC4R gene itself are among the most common single-gene causes of severe obesity, though most people with obesity do not have them.
Setmelanotide (Imcivree) activates MC4R directly. It is approved only for specific upstream defects and certain other conditions, not for MC4R variants in general or common obesity.
Genetic testing for obesity is ordered by specialists when severe obesity starts very early or runs in a family pattern.
Why it matters
MC4R explains why a small group of people need a very different treatment approach than standard weight-loss medicines.
Related terms
Sources
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