Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.07.241851v1?rss=1 Authors: Martin Alonso, A., Cork, S. C., Ma, Y., Arnold, M., Herzog, H., Bloom, S. R., Distaso, W., Murphy, K., Salem, V. Abstract: Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity mediated by the neuropeptide Y (NPY) Y2 receptor (Y2R). However, the neuronal pathways by which PYY3-36 acts to supress appetite are unclear. Determining how the PYY3-36 system physiologically regulates food intake may help exploit its therapeutic potential. Here we demonstrate that germline and post-natal targeted knockdown of the Y2R in the afferent vagus nerve inhibits the anorectic effects of physiologically-released PYY3-36, but not peripherally-administered higher doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is compensated for in the germline model. Loss of vagal Y2R signalling also alters meal patterning and accelerates gastric emptying. These results may facilitate the design of PYY-based anti-obesity agents. Copy rights belong to original authors. Visit the link for more info