The role of peptide YY in appetite regulation and obesity
Open accessAbstract
The last decade has witnessed a marked increase in our understanding of the importance of gut hormones in the regulation of energy homeostasis. In particular, the discovery that the gut hormone peptide YY 3–36 (PYY3–36) reduced feeding in obese rodents and humans fuelled interest in the role of PYY3–36 in body weight regulation. Pharmacological and genetic approaches have revealed that the Y2‐receptor mediates the anorectic effects of PYY3–36 whilst mechanistic studies in rodents identified the hypothalamus, vagus and brainstem regions as potential sites of action. More recently, using functional brain imaging techniques in humans, PYY3–36 was found to modulate neuronal activity within hypothalamic and brainstem, and brain regions involved in reward processing. Several lines of evidence suggest that low circulating PYY concentrations predispose towards the development and or maintenance of obesity. Subjects with reduced postprandial PYY release exhibit lower satiety and circulating PYY levels that correlate negatively with markers of adiposity. In addition, mice lacking PYY are hyperphagic and become obese. Conversely, chronic PYY3–36 administration to obese rodents reduces adiposity, and transgenic mice with increased circulating PYY are resistant to diet‐induced obesity. Moreover, there is emerging evidence that PYY3–36 may partly mediate the reduced appetite and weight loss benefits observed post‐gastric bypass surgery. Taken together these findings, coupled with the retained responsiveness of obese subjects to the effects of PYY3–36, suggest that targeting the PYY system may offer a therapeutic strategy to help treat obesity.
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PYY has been combined with GLP-1 to maximize central satiety pathways, modulating hypothalamus, brainstem, mid-brain, and reward-processing regions.
“Peptide YY or peptide tyrosine-tyrosine (PYY) has also been combined with GLP-1 to maximize the central pathways for satiety, modulating activity in the hypothalamus, brainstem, and mid-brain areas as well as regions of the brain involved in reward processing (Figure 1).47”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [47]
The unique properties of PYY together with the insulinotropic effects of GLP-1 receptor agonism may represent a novel weight-management approach in obesity and type 2 diabetes.
“These unique properties of PYY, in concert with the insulinotropic effects of GLP-1R agonism, may therefore represent a novel approach for weight management in both obesity and T2D.47”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [47]
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- Authors
- Karra, E., Chandarana, K., & Batterham, R. L.
- Affiliations
- University College London (GB)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2009-01
- Volume
- 587
- Issue
- 1
- Pages
- 19-25
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2670018
- OpenAlex
- W1509738237
- Cited by
- 336
- References
- 62
- Citations by year
- 2026: 16 · 2025: 45 · 2024: 29 · 2023: 16 · 2022: 24 · 2021: 28 · 2020: 15 · 2019: 16 · 2018: 17 · 2017: 17 · 2016: 9 · 2015: 12 · 2014: 24 · 2013: 15 · 2012: 15
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- peptide YY, PYY3-36, appetite regulation, obesity, gastrointestinal hormones, energy homeostasis, Y2 receptor, hypothalamus, vagus nerve, brainstem, satiety, postprandial hormone release, diet-induced obesity, bariatric surgery, weight loss, obesity treatment
- MeSH terms
- Animals, Appetite Regulation, Eating, Energy Metabolism, Humans, Obesity, Peptide Fragments, Receptors, Gastrointestinal Hormone, Gastric Bypass, Weight Loss, Peptide YY
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