PYY (3-36) protects against high fat feeding induced changes of pancreatic islet and intestinal hormone content and morphometry

A Sridhar, Dawood Khan, P R Flatt, N Irwin, R C Moffett

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Background: Prolonged high fat feeding negatively impacts pancreatic and intestinal morphology. In this regard, direct effects of PYY(3–36) on intestinal cell and pancreatic islet morphometry are yet to be fully explored in the setting of obesity. Methods: We examined the influence of 21-days twice daily treatment with PYY(3–36) on these parameters in mice fed a high fat diet (HFD). Results: PYY(3–36) treatment decreased food intake, body weight and circulating glucose in HFD mice. In terms of intestinal morphology, crypt depth was restored to control levels by PYY(3–36), with an additional enlargement of villi length. PYY(3–36) also reversed HFD-induced decreases of ileal PYY, and especially GLP-1, content. HFD increased numbers of PYY and GIP positive ileal cells, with PYY(3–36) fully reversing the effect on PYY cell detection. There were no obvious differences in the overall number of GLP-1 positive ileal cells in all mice, barring PYY(3–36) marginally decreasing GLP-1 villi cell immunoreactivity. Within pancreatic islets, PYY(3–36) significantly decreased alpha-cell area, whilst islet, beta-, PYY- and delta-cell areas remained unchanged. However, PYY(3–36) increased the percentage of beta-cells while also reducing percentage alpha-cell area. This was related to PYY(3-36)-induced reductions of beta-cell proliferation and apoptosis frequencies. Co-localisation of islet PYY with glucagon or somatostatin was elevated by PYY(3–36), with GLP-1/glucagon co-visualisation increased when compared to lean controls. Conclusion: PYY(3–36) exerts protective effects on pancreatic and intestinal morphology in HFD mice linked to elevated ileal GLP-1 content. General significance: These observations highlight mechanisms linked to the metabolic and weight reducing benefits of PYY(3–36).

Original languageEnglish
Article number130359
Pages (from-to)1-10
Number of pages10
JournalBBA - General Subjects
Issue number6
Early online date29 Mar 2023
Publication statusPublished (in print/issue) - 30 Jun 2023

Bibliographical note

Funding Information:
These studies were supported by Diabetes UK RD Lawrence Fellowship grant to RCM and Ulster University strategic funding.

Publisher Copyright:
© 2023 The Authors

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.


  • Enteroendocrine cell
  • High fat diet (HFD)
  • Ileum
  • Islet
  • NPY2 receptor
  • PYY(3–36)
  • Glucagon
  • Glucagon-Like Peptide 1/metabolism
  • Insulin-Secreting Cells/metabolism
  • Gastrointestinal Hormones/metabolism
  • Animals
  • Mice
  • Islets of Langerhans


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