Neuropeptide Y and peptide YY differentially modulate bitter- and fatty acid-evoked responses in human fungiform...

Numerous peptide hormones regulate feeding and metabolism via the brain and alimentary canal. Many of these peptides are also expressed, along with their cognate receptors, in the taste buds of the lingual epithelium. Among those present in the rodent oral cavity are peptides and receptors in the neuropeptide Y (NPY) family. Previous studies suggest that manipulation of NPY family peptide signaling can impact upon taste-related behavior, but it remains unclear whether these are mediated by changes in taste information processed by taste bud cells (TBCs), the primary sensory organs of the gustatory system, and whether human taste buds are similarly impacted by NPY family peptide signaling. In this report, we identify a complex modulatory role for NPY family peptides in shaping the tastant-evoked responses of human TBCs. Using a human fungiform taste bud cell line, we show that NPY and peptide YY (PYY), along with NPY receptor subtypes 1 and 2 (NPY1R and NPY2R), are expressed in TBCs. Importantly, NPY and PYY modulated the functional responses (assessed by calcium imaging and measurements of neurotransmitter release) of TBCs to bitter and fatty acid stimuli. The nature of modulation (i.e., enhancement or diminishment) was dependent not only on the peptide but also on the taste modality in question. Application of NPY1R and NPY2R antagonists indicated that the differential impacts of these peptides on TBC response parameters were mediated by differential NPY receptor activation. These data suggest that NPY family peptides directly and intricately modify gustatory sensory input by shaping TBC signaling.NEW & NOTEWORTHY The conventional view of feeding regulation by metabolic peptides largely comprises "top-down" peptidergic signaling via the hypothalamus incorporating pre- and postprandial information via the gut-brain axis. Here, we suggest a role for these peptides adjusting "bottom-up" taste information streams that impact food choice and intake. This novel dimension of peptidergic modulation may provide a more comprehensive understanding of taste, feeding, and metabolism that better informs diagnostic and therapeutic developments related to feeding and metabolic regulation.