The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36 on Food Intake

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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/241851v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@bef424org.highwire.dtl.DTLVardef@8e7d68org.highwire.dtl.DTLVardef@cb6757org.highwire.dtl.DTLVardef@1edb059_HPS_FORMAT_FIGEXP M_FIG C_FIG