Abstract

Peptide YY3-36 is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY3-36 is also present in murine as well as in human saliva. In mice, salivary PYY3-36 derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY3-36 induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO) mice, a sustained increase in PYY3-36 was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY3-36 resulted in a significant long-term reduction in food intake (FI) and body weight (BW). Thus this study provides evidence for new functions of the previously characterized gut peptide PYY3-36 suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity.

Highlights

  • A significant portion of metabolic polypeptides has been shown to be expressed in taste cells (TCs) or to be present in saliva

  • We provide evidence that the spectrum of metabolically relevant peptides present in murine and human saliva includes gut hormone PYY3-36 and that this peptide can be utilized to induced satiation

  • Because Peptide YY (PYY) is synthesized in the TCs of the circumvallate papillae (CV), it is conceivable that PYY3-36 is secreted from these cells into saliva

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Summary

Introduction

A significant portion of metabolic polypeptides has been shown to be expressed in taste cells (TCs) or to be present in saliva. Anatomical proximity of agonists and receptors suggested their putative roles in taste functions. Most of these polypeptides have been implicated in modulation of different tastes such as sweet [4,10,11,13], salty [14], sour [4,14], and umami [15]. Little is known whether these or other metabolic peptides that are present in saliva could play a more ‘traditional’ role regulating feeding behavior

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