Agouti-related peptide

Where it comes from

Made in

The NPY/AgRP neurons of the arcuate nucleus, and the adrenal

Sent out by

Fasting and ghrelin switch the neurons on; leptin, insulin and PYY switch them off

Acts on

• MC4R neurons of the paraventricular nucleus
• Other melanocortin targets

What it does

• Blocks alpha-MSH, so the fullness signal cannot get through: hunger ¹
• A single dose drives feeding for days, far longer than NPY ¹
• The AgRP neurons are the hunger neurons; activating them makes a fed mouse eat, silencing them in adults starves it ²

In medicine

• No medicine copies it or blocks it. Blood AgRP rises with fasting and is a research marker
• Setmelanotide works below the level at which AgRP acts: it activates MC4R directly, so the blockade AgRP imposes does not stand in its way. It is approved for obesity caused by faults in the melanocortin pathway ³

Beyond the body’s own use

• AgRP is studied in anorexia nervosa and in cachexia, conditions in which appetite is lost, and from the other direction in obesity; no AgRP preparation or blocker has been given to a person ¹
• Nothing containing AgRP is approved or obtainable outside the laboratory
• The clearest evidence of how much it matters comes from its neurons rather than the peptide: silencing the AgRP neurons of an adult mouse stops it eating altogether, while the same neurons can be removed in a newborn with little effect ²