The NPY family consists of three 36-amino acid peptides, neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP), which bind to the NPY receptor family of G protein-coupled receptors. Five NPY receptors, Y1, Y2, Y4, Y5 and y6, have been defined at the molecular level, and each signals primarily through Gi/o. Binding of NPY family peptides to NPY receptors mediates a variety of physiological effects, including promotion of food intake, decreased anxiety, inhibition of neurotransmitter and hormone release, vasoconstriction, and gut motility. Y4 binds preferentially to PP, with significant binding to NPY and PYY. Y4 plays a role in control of reproduction, as Y4-null, ob/ob double knockout mice have increased fertility relative to ob/ob mice with functional Y4. In addition, mice lacking Y4 display resistance to weight gain induced by high fat diet, and mice lacking both Y2 and Y4 are resistant to the enhanced weight gain exhibited by Y1-null mice fed a high fat diet.