Peptide YY (3-36)

Where it comes from

Made in

Made from PYY(1-36) in gut and blood by DPP-4

Sent out by

Rises after meals, highest after fat and protein

Acts on

• Arcuate nucleus (NPY/AgRP neurons)
• Vagal afferents

What it does

• Reduces food intake by quieting the NPY/AgRP hunger neurons ¹
• Slows gastric emptying and gut transit
• A satiety signal that is blunted in obesity ²

In medicine

• No approved medicine. An infusion cut what volunteers ate at a buffet by about 30% in obese and lean people alike, so obesity is not resistance to it ²
• Its rise after bariatric surgery helps explain the lasting loss of appetite

Beyond the body’s own use

• Long-acting Y2 agonists have reached phase 1 and 2 for obesity, often paired with semaglutide; the extra weight loss has been modest and nausea has held the dose down
• The 2002 finding that it cuts food intake at the concentrations a meal produces ¹ was contested for years, because other laboratories could not reproduce it in mice; the human infusion studies held ²
• Swallowed it is digested, so nasal and injected forms are what the trials have used