Peptides›Metabolic›Peptide YY (PYY)

Peptide YY (PYY)

/ Endogenous 36-residue peptide YY; pancreatic polypeptide family; Y2 receptor preferred (especially PYY 3-36)

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 4050.00 g·mol⁻¹

ALIAS · Peptide YY · PYY 3-36 · PYY-36 · Native PYY

—

Pass rate

Samples

Suppliers

Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

Terms in this page you can click for a plain-English popup: , , , , , , , .

§ A · Identity

Primary sequenceYPIKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-NH2

MW · 4050.00CLASS · Endogenous 36-residue peptide YY; pancreatic polypeptide family; Y2 receptor preferred (especially PYY 3-36)CATEGORY · Metabolic

Tier 3. Foundational gut satiety peptide isolated by Tatemoto in 1980. The bioactive truncated form PYY 3-36 (generated by DPP-4 cleavage of the parent PYY 1-36) is a Y2-receptor-selective agonist with proposed satiety actions. Several Y2-selective PYY analogs are in clinical development for obesity (Novo Nordisk NN9748 / amycretin and others) but none are FDA-approved.

§ B · Mechanism of action

PYY is a 36-residue C-terminally amidated peptide of the pancreatic polypeptide family (alongside NPY and pancreatic polypeptide). It is co-stored and co-secreted with GLP-1 from intestinal L cells in response to nutrient ingestion. The full-length PYY 1-36 binds all Y-family receptors (Y1, Y2, Y4, Y5) with broad pharmacology; the predominant circulating bioactive form is PYY 3-36, generated by N-terminal cleavage by dipeptidyl peptidase-4 (DPP-4) and selective for the Y2 receptor.

Y2-receptor activation in the arcuate nucleus of the hypothalamus inhibits NPY/AgRP orexigenic neurons, producing satiety. Peripheral Y2 signalling also slows gastric emptying. The Y2-selectivity of PYY 3-36 distinguishes it functionally from full-length PYY and from the related NPY peptide (which is Y1/Y5-preferring at orexigenic sites).

The pharmacology has driven development of long-acting Y2-selective PYY analogs (engineered for half-life extension and Y2 selectivity) as candidate obesity therapeutics - frequently in combination with GLP-1 analogs to leverage co-secretion biology.

§ C · Human clinical evidence

Tier 3 for the native peptide. The Batterham 2003 NEJM study reported that intravenous infusion of PYY 3-36 reduced ad libitum food intake by ~30% in lean and obese volunteers - a foundational result that motivated the analog drug-development programs. Attempted independent replications produced mixed results. No Phase 3 development of the native peptide. Engineered Y2-selective PYY analogs are in early clinical development.

§ D · Primary literature

PubMed12954742Batterham RL et al. — Inhibition of food intake in obese subjects by peptide YY3-36 · The New England Journal of Medicine · human-phase-1Intravenous infusion of PYY 3-36 reduced 24-hour food intake by ~30% in both lean and obese volunteers - foundational human pharmacology trial that launched PYY analog development.Limitations: Small n; acute infusion; subsequent independent replication attempts produced variable results.2003

PubMed6953409Tatemoto K et al. — Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion · Proceedings of the National Academy of Sciences USA · in-vitroOriginal isolation and partial sequencing of PYY from porcine intestine - foundational discovery establishing the pancreatic polypeptide family alongside PP and (subsequently) NPY.Limitations: Discovery paper; preclinical.1982

PubMed19064614Karra E et al. — The role of peptide YY in appetite regulation and obesity · The Journal of Physiology · reviewComprehensive review of PYY physiology and obesity pharmacology - L-cell co-secretion with GLP-1, Y2-receptor selectivity of PYY 3-36, and the analog drug-development rationale.Limitations: Narrative review; predates current Y2-selective long-acting analog readouts.2009

§ F · Safety signal

Native PYY 3-36 infusion in research settings has been associated with nausea (the dominant adverse effect, dose-related) and brief gastrointestinal discomfort. No long-term human safety database exists. Chronic Y2-receptor activation safety is uncharacterised.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The Batterham 2003 result has been described as difficult to replicate in subsequent studies, with various groups reporting smaller-than-original effects on food intake. The original effect size and the mechanistic clarity nonetheless launched the PYY-analog development programs that continue today.

Vendor-sold 'PYY' material may be supplied as either full-length PYY 1-36 or the truncated PYY 3-36, with very different receptor pharmacology. Buyers cannot assume the labelled form matches the bioactive form without checking the certificate of analysis - and vendor identity testing of peptides in this family has historically been variable.