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

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).