Peptide YY (1-36)

Where it comes from

Made in

L cells of the ileum, colon and rectum, with GLP-1

Sent out by

Food reaching the lower gut, in proportion to its calories, fat above all

Acts on

• Hypothalamus (arcuate nucleus)
• Vagus nerve
• Gut muscle and pancreas

What it does

• Slows gut transit (the “ileal brake”)
• Reduces appetite once trimmed to PYY(3-36) ¹
• Holds back pancreatic secretion

In medicine

• No medicine. PYY responses are low in obesity and high after gastric bypass, and the low fasting levels in obese volunteers were part of what first made it a target ²
• Measured in research alongside GLP-1, usually as a total that mixes this form with the trimmed one

Beyond the body’s own use

• Y2-selective analogues of the trimmed form have been tested in early obesity trials, alone and alongside semaglutide, with modest extra weight loss and a good deal of nausea; none is approved
• Nasal PYY(3-36) was trialled for weight loss and dropped because of nausea, which has been the limit on this whole family since the first infusion studies ²
• The hormone itself goes nowhere as a treatment: swallowed it is digested, injected it lasts minutes