Cited by 2,351Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyHypothalamic control of reproductive hormones

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Gut hormone PYY3-36 physiologically inhibits food intake

Batterham, Rachel L., Cowley, Michael A., Small, Caroline J., Herzog, Herbert, Cohen, Mark A., Dakin, Catherine L., Wren, Alison M., Brynes, Audrey E., Low, Malcolm J., Ghatei, Mohammad A., Cone, Roger D., Bloom, Stephen R.·2002·Nature

DOI 10.1038/nature00887

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Abstract

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

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Authors: Batterham, R. L., Cowley, M. A., Small, C. J., Herzog, H., Cohen, M. A., Dakin, C. L., Wren, A. M., Brynes, A. E., Low, M. J., Ghatei, M. A., Cone, R. D., & Bloom, S. R.
Affiliations: Imperial College London (GB)
Oregon National Primate Research Center (US)
Garvan Institute of Medical Research (AU)
Oregon Health & Science University (US)
Corresponding author: Bloom, Stephen R.
ORCID: Batterham, Rachel L.
Cowley, Michael A.
Herzog, Herbert
Low, Malcolm J.
Cone, Roger D.
Bloom, Stephen R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-08
Volume: 418
Issue: 6898
Pages: 650-654
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature00887
OpenAlex: W2091685843
Cited by: 2,351
References: 25
Citations by year: 2026: 54 · 2025: 64 · 2024: 55 · 2023: 53 · 2022: 73 · 2021: 106 · 2020: 73 · 2019: 92 · 2018: 97 · 2017: 70 · 2016: 73 · 2015: 98 · 2014: 97 · 2013: 121 · 2012: 121
FWCI: 38.36
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: PYY3-36, food intake regulation, arcuate nucleus, hypothalamus, proopiomelanocortin neurons, postprandial satiety, appetite, weight gain, c-fos, NPY neurons
MeSH terms: Action Potentials, Animals, Appetite, Arcuate Nucleus of Hypothalamus, Body Weight, Energy Intake, Electrophysiology, Feeding Behavior, Humans, Injections, Intraperitoneal, Injections, Intraventricular, Male, Mice, Inbred C57BL, Neurons, Peptide Fragments, Pro-Opiomelanocortin, Signal Transduction, Proto-Oncogene Proteins c-fos, Rats, Wistar, Gene Deletion, Receptors, Neuropeptide Y, Mice, Knockout, Peptide YY, Leptin, Mice, Rats

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Gut hormone PYY3-36 physiologically inhibits food intake

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