Can Satiety Peptides Like GLP-1 Change How Food Tastes? A Mouse Study on PYY and Exendin-4 | Research

The takeaway

Delivering the satiety peptides PYY and exendin-4 directly to the mouths of mice changed their taste responsiveness across multiple flavors, suggesting these hormones may influence food intake by altering taste perception itself.

Multiple taste qualities altered
Oral delivery of satiety peptides PYY and exendin-4 changed mouse taste responses across several flavor types, showing broad sensory modulation rather than affecting just one taste.

What the researchers found

Using adeno-associated virus vectors to deliver PYY and exendin-4 encoding genes to the salivary glands of wild-type male mice, researchers found that oral presence of these satiety peptides significantly altered taste-related behavioral responsiveness across multiple taste qualities. In vitro experiments on isolated taste bud cells confirmed that PYY and exendin-4 directly influence the responsiveness of these primary sensory cells.

This builds on previous work showing that PYY knockout mice had altered taste responsiveness and that restoring PYY expression in salivary glands rescued normal taste behavior. The current study extends these findings to normal mice with intact peptide signaling, demonstrating that exogenous peptide application can modulate taste even when the endogenous system is already functional.

Why it matters

Millions of people now take GLP-1 receptor agonists like semaglutide and report changes in how food tastes or reduced interest in certain foods. This study offers a biological explanation: GLP-1 pathway signaling can directly modulate taste bud cells. If satiety peptides don't just suppress appetite centrally but also change peripheral taste perception, it opens an entirely new dimension of how these drugs affect eating behavior — and potentially a new target for food intake modulation.

The numbers in context

Significant effect on multiple taste qualities; in vitro taste bud cell responsiveness changes

How the study worked

Researchers used adeno-associated virus (AAV) gene therapy to deliver genes encoding exendin-4 (a GLP-1 receptor agonist) and/or PYY to the salivary glands of male wild-type C57BL mice. This caused the mice to produce these peptides in their saliva, delivering them directly to taste buds during feeding. Taste responsiveness was measured using behavioral assays across multiple taste qualities. Additionally, the researchers tested the direct effects of these peptides on isolated taste bud cells in vitro.

Who was studied

Male wild-type C57BL mice

What this study cannot tell us

Only male mice were studied, so sex-specific differences in taste modulation are unknown. The AAV gene therapy delivery method is a research tool, not a clinically translatable approach. The abstract doesn't report specific quantitative data on the magnitude of taste changes. The study can't distinguish how much of the observed effect comes from PYY versus exendin-4 individually versus their combination.

How to read the evidence

Rated preliminary: novel and well-designed mechanistic animal study with both in vivo and in vitro components, but uses a non-translatable delivery method (AAV gene therapy), only male mice, and limited quantitative data in the abstract.

When this study was published

Published in 2025 in Neuropharmacology. This is very recent research contributing to an emerging understanding of how GLP-1 pathway signaling extends to the peripheral taste system.

The bigger picture

The taste system has traditionally been studied separately from gut hormone signaling. This study bridges those fields by showing that satiety peptides like GLP-1 agonists and PYY can act directly on taste buds to alter taste perception. As GLP-1 drugs become the dominant obesity treatment worldwide, understanding their peripheral sensory effects — not just their central appetite suppression — becomes increasingly important for predicting patient experiences and potentially developing new taste-targeted therapies.

Questions still open

Do patients on injectable GLP-1 agonists experience measurable changes in taste perception, and could this contribute to their reduced food intake?
Could taste bud-targeted delivery of satiety peptides be developed as a standalone approach to modulate food preferences?
Are there sex differences in how satiety peptides modulate taste, given that only male mice were tested?

Common questions

Could GLP-1 drugs like semaglutide be changing how food tastes to people?

This study suggests it's biologically plausible. Taste buds have receptors for GLP-1 and PYY, and delivering these peptides to the mouths of mice directly altered their taste responses. Many patients on GLP-1 drugs do report that food tastes different, and this research provides a potential mechanism for that experience.

Why did the researchers use gene therapy instead of just putting the peptides in the mice's mouths?

Gene therapy allowed the mice's own salivary glands to continuously produce the peptides, ensuring a steady supply directly to the taste buds during normal eating. This approach mimics what would happen if these peptides were naturally present in saliva, rather than just a brief exposure.

Read the original research

Exogenous oral application of PYY and exendin-4 impacts upon taste-related behavior and taste perception in wild-type mice.

Neuropharmacology, 272, 110408

View on PubMed ↗Publisher’s paper ↗

Citation

Iyer, Satya; Montmayeur, Jean-Pierre; Zolotukhin, Sergei; Dotson, Cedrick D. (2025). Exogenous oral application of PYY and exendin-4 impacts upon taste-related behavior and taste perception in wild-type mice.. Neuropharmacology, 272, 110408. https://doi.org/10.1016/j.neuropharm.2025.110408