Peptide YY

Peptide YY is a 36-amino-acid hormone released from L-cells in the lower gut after eating. Circulating levels rise in proportion to meal calories, and it acts as a satiety signal that tells the brain you are full. It is a research compound and physiological hormone, not an approved weight-loss drug.

They are opposites. Ghrelin is the hunger hormone that peaks before meals to drive you to eat, while PYY is a fullness hormone that rises after meals to reduce appetite. In appetite research the two are often studied together as a push-pull system regulating food intake.

PYY is secreted as PYY 1-36, then the enzyme DPP-4 trims it to PYY 3-36. That shorter form is selective for the Y2 receptor and is the fragment responsible for suppressing appetite. In Batterham's 2002 Nature study, infusing PYY 3-36 to normal post-meal levels reduced food intake by about 33% over 24 hours.

Two problems. The native peptide clears from the blood in minutes, so effects are brief, and the doses needed to curb appetite tend to cause nausea. Early obesity programs stalled on these limits, which is why interest has shifted toward longer-acting, better-tolerated analogues rather than native PYY.

Yes, and this is the most active line of research. PYY and GLP-1 are co-released from the same gut cells, and Neary's 2005 study found they inhibit food intake additively, with about a 27% reduction in energy intake when given together in humans. That additive effect is the rationale behind PYY plus GLP-1 co-agonist development.

Roux-en-Y gastric bypass sharply raises post-meal PYY and GLP-1, favoring an anorectic, low-appetite state. le Roux's work identified this gut-hormone surge as a key reason bypass patients eat less and keep weight off, whereas patients losing similar weight through gastric banding do not show the same rise.