Affinage

PYY

Peptide YY · UniProt P10082

Length
97 aa
Mass
11.1 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PYY is a gut-derived anorexigenic peptide hormone released from intestinal L cells in response to luminal nutrients (fatty acids, glucose, amino acids), short-chain fatty acids (via FFA2 receptors and HDAC inhibition), sweet/bitter taste receptor signaling (T1R2/T1R3 and gustducin-coupled pathways), and angiotensin II (via AT1R), and is proteolytically converted by DPP-IV from the non-selective Y1/Y2 agonist PYY(1-36) to the Y2-selective form PYY(3-36) (PMID:8097274, PMID:7984499, PMID:25109781, PMID:21540445, PMID:27447725). PYY(3-36) inhibits food intake centrally by acting on Y2 receptors in the hypothalamic arcuate nucleus—suppressing NPY neurons and disinhibiting POMC neurons—and in circumventricular organs (area postrema, subfornical organ), with redundant vagal and humoral input pathways contributing to brainstem neuronal activation and conditioned taste aversion (PMID:12167864, PMID:16054059, PMID:20646064). Peripherally, PYY exerts Y2-mediated direct inhibition of vagal motor neurons in the dorsal motor nucleus (gated by intracellular cAMP levels), slows intestinal transit through serotonergic-opioid pathways, and acts in a paracrine Y1-dependent manner to suppress colonic epithelial ion transport and fluid secretion (PMID:9249552, PMID:19622099, PMID:15010361, PMID:23992397). PYY also functions as an intra-islet regulator—expressed in alpha cells and beta cells—where it enhances glucose-stimulated insulin secretion and promotes beta-cell mass, and it exerts antilipolytic effects in adipocytes via Y1 receptors (PMID:27117413, PMID:26125465, PMID:8393293).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1988 Medium

    Establishing how PYY secretion is directly regulated resolved a key question about the physiological triggers for this L-cell hormone: fatty acids and cAMP-linked pathways were identified as direct secretagogues.

    Evidence Primary canine colonic L-cell cultures with pharmacological stimulation

    PMID:3377082

    Open questions at the time
    • Signaling cascade downstream of fatty acid sensing not identified
    • Relevance to human L cells not tested
  2. 1991 High

    Identifying the receptor subtype mediating PYY actions in the pancreas revealed that PYY signals through Y1 receptors on pancreatic vascular smooth muscle, suggesting a vascular rather than direct endocrine mechanism.

    Evidence Autoradiographic receptor localization and competitive binding with Y1-selective agonist in rat pancreas

    PMID:1847590

    Open questions at the time
    • Direct islet cell receptor expression not characterized
    • Functional consequence of vascular Y1 activation on islet blood flow not measured
  3. 1993 High

    Two discoveries established that DPP-IV-mediated cleavage generates a Y2-selective form PYY(3-36), and that PYY receptors in adipocytes mediate regional antilipolytic effects, defining both a key processing step and a peripheral metabolic action.

    Evidence In vitro DPP-IV enzymatic assay with receptor binding [PMID:8097274]; radioligand binding and lipolysis assay on human adipocytes from multiple depots [PMID:8393293]

    PMID:8097274 PMID:8393293

    Open questions at the time
    • In vivo DPP-IV processing kinetics not measured
    • Y receptor subtype mediating adipocyte antilipolysis not definitively assigned
  4. 1994 High

    Purification of both PYY(1-36) and PYY(3-36) from intestinal tissue and demonstration of their distinct receptor selectivities confirmed that proteolytic processing is a physiological mechanism controlling receptor subtype engagement.

    Evidence Peptide purification from rabbit intestinal mucosa with receptor binding displacement assays

    PMID:7984499

    Open questions at the time
    • Relative circulating concentrations of both forms in fed versus fasted states not quantified
  5. 1996 Medium

    Demonstrating transient PYY co-expression with insulin and glucagon in dividing embryonic pancreatic cells suggested PYY marks multipotent endocrine precursors, opening the question of whether PYY has a developmental function.

    Evidence Immunohistochemistry with BrdU S-phase labeling across developmental stages in rat and mouse pancreas

    PMID:8756753

    Open questions at the time
    • No loss-of-function test for PYY in pancreatic development
    • Whether PYY expression is functionally required or merely a lineage marker is unresolved
  6. 1997 High

    Electrophysiological and pharmacological studies revealed that PYY directly inhibits vagal motor neurons via Y2 receptors and bidirectionally controls gastric motility via Y1/Y2 in the dorsal vagal complex, establishing central autonomic circuits as key effector pathways.

    Evidence Brain stem slice electrophysiology with synaptic blockade and Y2-selective agonist [PMID:9249552]; DVC microinjection with gastric motility recording [PMID:9198086]

    PMID:9198086 PMID:9249552

    Open questions at the time
    • Whether circulating PYY achieves sufficient concentrations at the DVC to reproduce these effects physiologically was not established
  7. 1997 Medium

    Discovery that PYY upregulates intestinal fatty acid-binding protein and stimulates apolipoprotein AIV secretion post-transcriptionally extended PYY's role beyond motility/appetite to intestinal lipid handling.

    Evidence In situ hybridization in intestinal hybrid cells [PMID:9139712]; mesenteric lymph fistula rat model with mRNA/protein comparison [PMID:9756495]

    PMID:9139712 PMID:9756495

    Open questions at the time
    • Receptor subtype mediating apo AIV stimulation not identified
    • Post-transcriptional mechanism (mRNA stability vs. translational) not resolved
  8. 2000 High

    Structural studies revealed that PYY(1-36) and PYY(3-36) adopt distinct solution conformations correlated with Y1/Y2 selectivity, and that the functional receptor-binding state is membrane-associated with a stabilized C-terminal helix.

    Evidence CD, NMR, and sedimentation equilibrium on PYY variants [PMID:10898754]; NMR of micelle-bound pPYY [PMID:15178255]

    PMID:10898754 PMID:15178255

    Open questions at the time
    • No receptor-bound co-crystal or cryo-EM structure
    • How N-terminal truncation alters membrane association and receptor docking at atomic detail remains unknown
  9. 2002 High

    The landmark demonstration that PYY(3-36) inhibits food intake via arcuate nucleus Y2 receptors—suppressing NPY neurons and activating POMC neurons—established the central satiety mechanism.

    Evidence Y2r knockout mice, peripheral and intra-arcuate injection, electrophysiology, c-Fos mapping, and human infusion in a single study

    PMID:12167864

    Open questions at the time
    • Whether Y2R in the arcuate is sufficient versus necessary for the full anorectic response was not resolved by this study alone
  10. 2005 High

    Vagotomy and brain mapping studies revealed that PYY(3-36) anorexia does not require the vagus but involves brainstem aversive circuits (area postrema, NTS), while subsequent lesion studies showed the area postrema and subfornical organ act redundantly as central access points.

    Evidence Vagotomy with c-Fos and conditioned taste aversion [PMID:16054059]; combinatorial AP/SFO lesions with vagotomy and c-fos mapping [PMID:20646064]; radiolabeled PYY biodistribution [PMID:17952639]

    PMID:16054059 PMID:17952639 PMID:20646064

    Open questions at the time
    • Relative contribution of aversive versus homeostatic satiety signaling to total food intake reduction remains unquantified
    • Neuronal cell types in area postrema responding to PYY not fully characterized
  11. 2006 Medium

    Co-localization of gustducin with PYY in colonic L cells and functional bitter taste receptor signaling in these cells revealed that chemosensory taste pathways regulate PYY secretion, later extended to sweet taste receptor T1R2/T1R3 in humans.

    Evidence Immunofluorescence co-localization and Ca2+ imaging in human intestinal endocrine cells [PMID:16728727]; randomized controlled human study with T1R2/T1R3 antagonist lactisole [PMID:21540445]

    PMID:16728727 PMID:21540445

    Open questions at the time
    • Quantitative contribution of taste receptor pathways versus nutrient transporters to total postprandial PYY release is unknown
    • Downstream signaling cascade from gustducin to granule exocytosis not delineated
  12. 2009 High

    The finding that PYY modulation of vagal GABAergic transmission requires elevated cAMP revealed a gating mechanism: PYY's inhibition of vagal circuits is context-dependent, only operative when neurons are already activated by other signals.

    Evidence Whole-cell patch-clamp of DMV neurons with forskolin and physiological cAMP elevators (CCK, TRH)

    PMID:19622099

    Open questions at the time
    • In vivo confirmation that cAMP-dependent gating determines PYY efficacy on vagal output is lacking
    • Whether this gating extends to other brain regions expressing Y2R is untested
  13. 2013 High

    Using PYY knockout tissue and receptor antagonists, paracrine PYY signaling through epithelial Y1 receptors was shown to inhibit colonic ion transport, establishing PYY as a local regulator of fluid secretion in addition to its endocrine roles.

    Evidence Ussing chamber on PYY-/- mouse colonic and jejunal mucosa with Y1 antagonist

    PMID:23992397

    Open questions at the time
    • Whether this paracrine axis is dysregulated in inflammatory bowel disease is unknown
    • Quantitative contribution to whole-body fluid balance not assessed
  14. 2014 High

    SCFA-driven PYY secretion was mechanistically dissected: propionate acts through FFA2 in mice, while in human cells SCFAs primarily induce PYY gene transcription via HDAC inhibition; fermentable carbohydrates expand PYY-producing cell populations via FFAR2.

    Evidence FFA2 knockout mice with in vivo and crypt culture validation [PMID:25109781]; HDAC inhibitor studies in human L-cell models [PMID:29311617]; Ffar2 KO with dietary inulin and organoids [PMID:28123937]

    PMID:25109781 PMID:28123937 PMID:29311617

    Open questions at the time
    • Relative importance of FFA2 versus HDAC pathways in intact human gut in vivo is unresolved
    • Chromatin targets of SCFA-mediated HDAC inhibition at the PYY locus not mapped
  15. 2016 High

    Multiple studies expanded PYY's regulatory inputs and outputs: angiotensin II via AT1R on L cells triggers PYY release that limits colonic fluid secretion via Y1; TLR/NF-κB signaling enhances PYY expression; and elevated PYY after gastric bypass normalizes islet function independently of GLP-1.

    Evidence AT1R agonism with Ca2+ imaging and Ussing chamber in mouse/human colon [PMID:27447725]; NF-κB reporter in human L-cell model [PMID:27405092]; GK rat RYGB with PYY neutralization and GLP-1R antagonist [PMID:27117413]

    PMID:27117413 PMID:27405092 PMID:27447725

    Open questions at the time
    • Whether AT1R-PYY axis is physiologically relevant in hypertension or ACE-inhibitor therapy is untested
    • Molecular mechanism by which PYY normalizes islet morphology is not defined
  16. 2017 Medium

    Intra-islet PYY localized in alpha cells was shown to enhance insulin secretion and beta-cell mass, with DPP-IV processing controlling local PYY activity, revealing an autocrine/paracrine islet circuit distinct from gut-derived PYY.

    Evidence Immunohistochemistry, sitagliptin DPP-IV inhibition, islet secretion in rodent and human islets [PMID:28892258]; transgenic beta-cell PYY overexpression with glucose tolerance and beta-cell proliferation [PMID:26125465]

    PMID:26125465 PMID:28892258

    Open questions at the time
    • Y receptor subtype mediating islet PYY effects not definitively identified
    • Whether intra-islet PYY contributes meaningfully to glycemic control in non-surgical settings is unclear
    • Single-lab findings for intra-islet circuit
  17. 2022 Medium

    The finding that GIPR agonism reduces PYY(3-36)-induced conditioned taste aversion via co-expressed GIPR/NPY2R neurons in the area postrema dissociated PYY's aversive from its hypophagic signaling, with therapeutic implications for incretin-based anti-obesity drugs.

    Evidence Conditioned taste avoidance in mice, cFos whole-brain analysis, receptor co-expression mapping in area postrema

    PMID:35499381

    Open questions at the time
    • Whether GIPR-NPY2R interaction occurs at the intracellular signaling level or involves separate downstream circuits is unknown
    • Human translation of the GIPR–PYY interaction not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of PYY bound to Y2R, the precise chromatin and transcriptional regulation of the PYY gene in L cells, the relative physiological contribution of aversive versus homeostatic pathways to PYY-mediated satiety in humans, and the mechanism by which PYY promotes beta-cell proliferation.
  • No receptor-bound structural model of PYY–Y2R complex
  • Transcriptional regulation of the PYY gene locus largely unmapped
  • Mechanism of PYY-driven beta-cell proliferation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 5 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 3 R-HSA-8963743 Digestion and absorption 3
Partners
AGTR1DPP4FFAR2GNAT3NPY1RNPY2RTAS1R2

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PYY(3-36) inhibits food intake via the NPY Y2 receptor (Y2R) in the arcuate nucleus: peripheral injection inhibits feeding in wild-type but not Y2r-null mice, increases c-Fos in the arcuate nucleus, decreases hypothalamic NPY mRNA, inhibits electrical activity of NPY nerve terminals thereby activating adjacent POMC neurons, and intra-arcuate injection of PYY(3-36) inhibits food intake. Y2r knockout mice (genetic epistasis), peripheral and intra-arcuate injection, c-Fos immunoreactivity, in situ hybridization, electrophysiology, human infusion study Nature High 12167864
1993 Dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal dipeptide Tyr-Pro from PYY(1-36) to generate PYY(3-36), converting a non-selective Y1/Y2 agonist into a highly selective Y2 receptor agonist; DPP-IV is present on endothelial surfaces and brush border membranes and is the only enzyme tested capable of performing this cleavage. In vitro enzymatic assay with purified DPP-IV and PYY substrate; receptor binding assays Medizinische Klinik High 8097274
1994 Two endogenous molecular forms of PYY exist in vivo—PYY(1-36) and PYY(3-36)—with distinct receptor selectivity: PYY(1-36) is an unselective Y1/Y2 agonist whereas PYY(3-36) is a highly selective Y2 agonist, demonstrating that proteolytic processing controls receptor subtype selectivity. Peptide purification from rabbit intestinal mucosa, primary structure determination (sequencing), receptor binding displacement assays Peptides High 7984499
2000 PYY(1-36), [Pro34]PYY (Y1-selective), and PYY(3-36) (Y2-selective) adopt distinct solution conformations (differing helicities by CD and NMR) that correlate with their receptor subtype binding affinities, suggesting conformation contributes to Y receptor subtype selectivity. Circular dichroism, 1H-NMR, sedimentation equilibrium, receptor binding (Y1- and Y2-transfected cells) American journal of physiology. Gastrointestinal and liver physiology High 10898754
2004 PYY adopts the PP-fold in solution but binds to Y receptors from a membrane-associated (micelle-bound) state in which the N-terminus is free and the C-terminal helix is stabilized; micelle-bound pPYY and pNPY are structurally much more similar than their solution structures, explaining their similar receptor binding profiles at Y1/Y2 receptors. NMR structure of pPYY in solution and bound to DPC micelles; heteronuclear NOE, generalized order parameters S2 Journal of molecular biology High 15178255
2005 The anorectic effect of peripherally administered PYY(3-36) is not dependent on the vagus nerve, but activates neurons in the area postrema and nucleus tractus solitarius (brainstem areas mediating aversive stimuli) and produces conditioned taste aversion in mice, suggesting its food-intake inhibition partly involves induction of an aversive response. Vagotomy, c-Fos immunoreactivity, conditioned taste aversion assay in mice Cell metabolism High 16054059
1997 PYY and the Y2-selective agonist PYY(13-36) directly inhibit approximately 50% of dorsal motor nucleus of the vagus (DMN) neurons via Y2 receptors, including under synaptic blockade, providing a direct mechanism by which circulating PYY suppresses vagally mediated digestive functions. In vivo and in vitro brain stem slice electrophysiology, synaptic blockade, Y2-selective agonist pharmacology The American journal of physiology High 9249552
1997 PYY controls gastric motility via differential action at Y1 and Y2 receptors in the dorsal vagal complex (DVC): Y2 agonist applied to the DVC suppresses TRH-stimulated gastric motility (mimicking peripheral PYY), while Y1 agonist stimulates motility from basal conditions, indicating receptor-specific bidirectional control. Microinjection into DVC, gastric motility recording, Y1 and Y2 selective agonists Neurogastroenterology and motility Medium 9198086
2009 NPY and PYY modulate GABAergic inhibitory synaptic transmission onto dorsal motor nucleus of the vagus (DMV) neurons via presynaptic Y1 and Y2 receptors, but only when intracellular cAMP levels are elevated (by forskolin, CCK-8s, TRH, or vagal deafferentation); under low resting cAMP, neither peptide inhibits evoked IPSCs. Whole-cell patch-clamp recordings from identified DMV neurons, cAMP manipulation, spontaneous and miniature current analysis, receptor-selective agonists Neurogastroenterology and motility High 19622099
2004 PYY slows intestinal transit via serotonergic (5-HT) neurotransmission that is coupled to a downstream opioid (naloxone-sensitive) pathway; both pathways are localized to the efferent (proximal gut) limb and 5-HT-induced slowing of transit is itself naloxone-reversible. Fistulated dog model with compartmentalized gut perfusion, selective receptor antagonists (ondansetron, naloxone), intestinal transit measurement American journal of physiology. Gastrointestinal and liver physiology Medium 15010361
1991 PYY receptors in rat pancreas are Y1-type receptors localized predominantly on vascular smooth muscle cells (and to a lesser extent endothelial cells), as shown by autoradiography with 125I-Tyr36-PYY and displacement by the Y1-selective agonist [Leu31,Pro34]NPY. Slide-mount autoradiography, collagenase-isolated vascular fractions, competitive binding, light- and electron-microscopic autoradiography The American journal of physiology High 1847590
2014 Propionate stimulates PYY and GLP-1 secretion from colonic L cells via free fatty acid receptor 2 (FFA2/GPR43): propionate-induced gut hormone release is significantly attenuated in FFA2-knockout mice both in primary colonic crypt cultures and in vivo (portal and jugular vein measurements after intra-colonic infusion). FFA2 knockout mice, primary murine colonic crypt cultures (in vitro), in vivo intra-colonic infusion with portal/jugular vein sampling International journal of obesity (2005) High 25109781
2016 Fermentable carbohydrate (inulin) acts via FFAR2 to drive an 87% increase in PYY-producing cell density in the colon, reducing food intake and preventing diet-induced obesity; this effect is absent in Ffar2-knockout mice. Ffar2 knockout mice, dietary supplementation, enteroendocrine cell density measurement, intestinal organoids and colonic cultures Molecular metabolism High 28123937
2018 SCFAs (propionate and butyrate) strongly increase PYY gene expression and hormone secretion in human enteroendocrine cells predominantly via histone deacetylase (HDAC) inhibitory activity, with minor contribution of FFA2 (GPR43); this transcriptional stimulation is specific to human-derived cell models and not reproduced in murine primary cultures due to differences in PYY gene structure. Human cell lines and intestinal primary cultures, HDAC inhibition assays, FFA2 pharmacology, gene expression and secretion measurements Scientific reports Medium 29311617
2016 TLR stimulation increases PYY expression in enteroendocrine L cells via an NF-κB-dependent pathway, additive to butyrate effects; butyrate also upregulates TLR expression (including TLR4), enhancing the NF-κB response to TLR stimulation and thus linking microbiota sensing to PYY production. Human L-cell model with NF-κB reporter, TLR agonists, butyrate treatment, gene expression analysis Cellular microbiology Medium 27405092
2006 The taste-signaling G protein α-gustducin co-localizes with PYY and GLP-1 in enteroendocrine L cells of the human colon; stimulation with the bitter compound phenylthiocarbamide (a hT2R38 ligand) induces rapid intracellular Ca2+ increases in human intestinal endocrine cell lines, indicating gustducin-coupled chemosensory receptors mediate PYY secretion signals. Double-labeling immunofluorescence, serial section immunostaining, RT-PCR, intracellular Ca2+ imaging American journal of physiology. Gastrointestinal and liver physiology Medium 16728727
2011 The intestinal sweet taste receptor T1R2/T1R3 (coupled through α-gustducin) is functionally involved in glucose-stimulated PYY and GLP-1 secretion in humans: blockade with the T1R2/T1R3 antagonist lactisole significantly reduces postprandial PYY and GLP-1 release after intragastric and intraduodenal glucose administration. Randomized double-blind placebo-controlled crossover human study, lactisole pharmacology, plasma hormone measurement American journal of physiology. Endocrinology and metabolism Medium 21540445
2016 Angiotensin II stimulates PYY and GLP-1 secretion from colonic L cells via the Ang II type 1 receptor (AT1R), which is exclusively expressed in colonic L cells; AT1R activation raises intracellular calcium in L cells, and the released PYY acts on epithelial Y1 receptors to reduce ion transport (short-circuit current), thereby limiting fluid secretion into the colonic lumen. Primary cultures of mouse and human colon, candesartan antagonist, live-cell GCaMP3 calcium imaging, Ussing chamber electrophysiology, Y1 receptor antagonist Endocrinology High 27447725
2016 Elevated circulating PYY following Roux-en-Y gastric bypass (RYGB) restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology in diabetic GK rats; serum from RYGB animals mimics these effects on isolated islets, and this is reversed by PYY neutralization but not GLP-1 receptor antagonism. GK rat RYGB model, isolated islet culture with RYGB serum, PYY neutralization, GLP-1 receptor antagonist, chronic PYY in vitro exposure Cell reports High 27117413
2017 Intra-islet PYY (localized in alpha-cells) is regulated by DPP-IV activity; DPP-IV inhibition by sitagliptin enhances glucose-stimulated insulin secretion (GSIS) via local PYY rather than GLP-1; chronic PYY application directly enhances GSIS in rodent and diabetic human islets; RYGB strongly increases islet PYY content. Immunohistochemistry, gene expression, DPP-IV inhibition with sitagliptin, islet secretion studies, radioimmunoassay Diabetes, obesity & metabolism Medium 28892258
2015 Pancreatic islet beta-cell-derived PYY improves glucose homeostasis by increasing beta-cell mass and insulin secretion; transgenic overexpression of PYY in beta-cells (Pyy-tg/Rip-Cre mice) leads to elevated serum insulin, improved glucose tolerance, increased beta-cell proliferation, and altered expression of genes important for beta-cell function. Transgenic mouse model (Rip-Cre driven PYY overexpression), glucose tolerance tests, beta-cell mass quantification, gene expression analysis Endocrinology Medium 26125465
1988 PYY secretion from primary colonic L cells is stimulated by sodium oleate (fatty acid) in a dose-dependent manner, as well as by bombesin, epinephrine, and forskolin (cAMP elevation), but not by carbachol, establishing fatty acids and cAMP-linked pathways as direct secretagogues. Primary culture of canine colonic PYY cells on collagen, elutriation-based enrichment, secretion assay with pharmacological agents The American journal of physiology Medium 3377082
1997 PYY upregulates intestinal fatty acid-binding protein (I-FABP) transcripts specifically in differentiated enterocytes via high-affinity PYY receptors (IC50 5-50 pM), acting through a post-transcriptional or transcriptional mechanism that is confined to terminally differentiated villar cells and does not affect mRNA in proliferating cells. Quantitative in situ hybridization on intestinal epithelial hybrid cell lines, competitive binding autoradiography, ribonuclease protection assay, BrdU incorporation The Journal of biological chemistry Medium 9139712
1998 PYY stimulates intestinal apolipoprotein AIV (apo AIV) synthesis and lymphatic secretion by a post-transcriptional mechanism: intravenous PYY (75-200 pmol/kg/h) increases apo AIV output up to 3.5-fold and raises jejunal mucosal apo AIV synthesis by 60% without affecting apo AIV mRNA levels. Mesenteric lymph fistula rat model, intravenous PYY infusion, apo AIV protein output measurement in lymph, mucosal synthesis assay, mRNA analysis The American journal of physiology Medium 9756495
2007 After peripheral (i.p.) injection, PYY(3-36) distributes to the area postrema (and subfornical organ and median eminence) in the brain, with near-background signals in all other brain structures including hypothalamic nuclei, suggesting the anorectic effect of peripheral PYY(3-36) is mediated primarily through circumventricular organs rather than direct hypothalamic action. Whole-body autoradiography and brain section autoradiography after i.p. and i.v. injection of 125I-labeled PYY(3-36) and analogs in rats Journal of molecular neuroscience Medium 17952639
2010 The anorectic effect of peripheral PYY(3-36) requires intact area postrema (AP) and subfornical organ (SFO) acting redundantly (ablation of either alone is insufficient), and also partially requires subdiaphragmatic vagal input; vagotomy further reveals that AP and SFO neuronal activation by peripheral PYY is partly vagally driven. Lesion of AP, SFO, or both combined; subdiaphragmatic vagotomy; c-fos mRNA brain mapping; food intake measurement in rats The European journal of neuroscience High 20646064
2007 PYY(3-36) activates neurons in the arcuate nucleus (ARC), commissural and gelatinous NTS, and area postrema; approximately 10% of Fos+ neurons in the cmNTS are catecholaminergic (TH+), indicating that PYY(3-36) inhibits feeding partly through activation of ARC neurons and hindbrain catecholaminergic circuits. Peripheral PYY(3-36) injection in rats, c-Fos immunoreactivity in multiple brain regions, tyrosine hydroxylase double-labeling Peptides Medium 18082288
2008 Central PYY-immunoreactive neurons are located exclusively in the gigantocellular reticular nucleus (Gi) of the rostral medulla in mouse, rat, and monkey; their axonal projections concentrate in the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and hypoglossal nucleus, and they receive input from orexin and MCH fibers, suggesting a role in energy homeostasis via visceral and autonomic circuits. Immunohistochemistry in NPY-knockout mouse (to eliminate NPY crossreactivity), NPY-preabsorbed antibody in rat, cross-species comparison, projection mapping The Journal of comparative neurology Medium 18022952
1993 PYY receptors in human adipocytes mediate antilipolytic effects; PYY (10^-7 M) inhibits lipolysis by 58% in femoral and 14% in pericolonic fat cells, correlating with regional PYY receptor density; this is an inhibitory system alongside the alpha2-adrenergic system. Radioligand binding (125I-PYY) on adipocyte membranes from multiple depots, lipolysis assay on isolated adipocytes The American journal of physiology Medium 8393293
2013 Endogenous PYY released from colonic L cells acts in a paracrine fashion via Y1 receptors to inhibit epithelial ion transport: L-glutamine-stimulated PYY release produces slow reductions in short-circuit current (Isc) in colonic and jejunal mucosa that are absent in PYY-/- tissue and blocked by Y1 receptor antagonist; the initial GLP-1-mediated Isc increase can be partially attributed to GLP-1 receptor activation. Ussing chamber voltage-clamp of mouse intestinal mucosae, PYY knockout tissue, selective Y1 and GLP-1 receptor antagonists, CaSR inhibitor British journal of pharmacology High 23992397
2022 GIP receptor (GIPR) agonism reduces PYY(3-36)-induced conditioned taste aversion (CTA) without affecting PYY-mediated hypophagia; GIPR and NPY2R are co-expressed on the same neurons in the area postrema; peripheral GIPR agonism reduces PYY-induced neuronal activity in the parabrachial nucleus (PBN), providing a mechanistic basis for reduced nausea. Conditioned taste avoidance in mice, central and peripheral administration, cFos whole-brain analysis, receptor co-expression in area postrema neurons Diabetes Medium 35499381
2009 PYY(3-36) (Y2 receptor agonist) inhibits diarrhea by two mechanisms: reducing intestinal fluid secretion and slowing colonic transit, both demonstrated in mouse models using a selective Y2 agonist alongside PYY(3-36). Mouse diarrhea models (dimethyl-PGE2, 5-HT, castor oil), intestinal fluid accumulation assay, colonic transit (fecal output) measurement, Y2-selective agonist comparison Peptides Medium 19925840
1996 PYY mRNA is transiently expressed in all early pancreatic endocrine cell types during embryogenesis (E12 onward), co-localizing with glucagon and insulin in multipotent precursor cells; PYY expression precedes NPY and PP, and actively-dividing triple-positive (insulin+glucagon+PYY) cells are consistent with a precursor role for PYY-positive endocrine cells. Immunohistochemistry, BrdU S-phase labeling, developmental staging in rat and mouse pancreas The journal of histochemistry and cytochemistry Medium 8756753
2015 GLP-1 and PYY are co-stored in separate secretory granules from neurotensin in intestinal L cells, yet all three peptides are co-secreted together from perfused small intestines and colonic crypt cultures in response to metabolite, neuropeptide, and hormonal stimuli; neurotensin acts synergistically with GLP-1 and PYY to decrease food intake and inhibit gastric emptying. FACS-sorted cell analysis, laser capture, confocal fluorescence microscopy, perfused intestine and crypt culture secretion assays, cell ablation studies, feeding and gastric emptying assays Endocrinology High 26469136

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 1697 12167864
2014 The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. International journal of obesity (2005) 611 25109781
2018 SCFAs strongly stimulate PYY production in human enteroendocrine cells. Scientific reports 330 29311617
2008 Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. American journal of physiology. Endocrinology and metabolism 323 18796545
2018 The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. American journal of physiology. Gastrointestinal and liver physiology 289 29494208
2012 A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology 258 23064014
2006 Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. American journal of physiology. Gastrointestinal and liver physiology 222 16728727
1999 GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. The American journal of physiology 193 10484511
2016 Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. Molecular metabolism 188 28123937
2011 The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. American journal of physiology. Endocrinology and metabolism 156 21540445
1983 Immunocytochemical identification of polypeptide YY (PYY) cells in the human gastrointestinal tract. Histochemistry 156 6341321
2005 Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice. Cell metabolism 155 16054059
2011 The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clinical nutrition (Edinburgh, Scotland) 139 21324568
2015 Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism. Endocrinology 115 26469136
2013 High protein intake stimulates postprandial GLP1 and PYY release. Obesity (Silver Spring, Md.) 114 23666746
2008 Weight regain after Roux-en-Y: a significant 20% complication related to PYY. Nutrition (Burbank, Los Angeles County, Calif.) 106 18725080
2000 Primary structures of PYY, [Pro(34)]PYY, and PYY-(3-36) confer different conformations and receptor selectivity. American journal of physiology. Gastrointestinal and liver physiology 104 10898754
2002 Structure and receptor binding of PYY analogs. Peptides 93 11825645
2016 TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways. Cellular microbiology 80 27405092
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