Neuropeptide Y (NPY)-induced feeding behavior in female rats: comparison with human NPY ([Met 17]NPY), NPY analog ([norLeu 4]NPY) and peptide YY

Abstract

Porcine neuropeptide Y (pNPY) administered into the third ventricle of the brain is known to elicit a powerful feeding response in steroid-treated ovariectomized and intact male rats. The present study compared the effects of pNPY and 3 structurally related peptides, human NPY (hNPY), an analog of NPY (NPY-A, [norLeu 4]NPY) and peptide YY (PYY) on feeding behavior in intact female rats. Intraventricular administration of pNPY, hNPY, NPY-A and PYY over a dose range of 0.5 to 10 μg evoked feeding behavior to a varying extent. Cumulative food intake during 60 and 120 min was increased in a dose-related fashion at 0.5 and 2.0 μg for the 4 peptides. Whereas the 10-μg dose of pNPY evoked a feeding response smaller than that seen after 2 μg, the responses to either 10 μg hNPY or 10 μg PYY were similar to that seen after 2 μg. The effects of these peptides on the time spent eating were quite different: while pNPY increased the time spent eating, this effect was not dose-related, whereas hNPY, NPY-A and PYY produced dose-related increments in the time spent eating. The most dramatic increment in local eating rate was observed after 2.0 μg pNPY, with lesser increments seen after 2.0 μg hNPY and NPY-A. This increased local eating was apparently responsible for the highest cumulative food intake observed. These results demonstrate that (a) 2 μg pNPY is equally effective in stimulating feeding behavior in intact female rats as it is in steroid-primed ovariectomized female and intact male rats; (b) like the other members of the pancreatic polypeptide family, the PYY-stimulated feeding response was smaller than seen after pNPY; (c) in general, the cumulative food intake response, when compared with that evoked by pNPY, is reduced after substitution of either single, as in hNPY and NPY-A, or multiple amino acids as in the case of the members of the pancreatic polypeptide family, including PYY and (d) surprisingly, unlike pNPY, the other peptides tested facilitate the time spent eating response in a dose-related fashion. Further studies are needed to identify those active moieties in pNPY and other polypeptides of the pancreatic polypeptide family that impart differential effects on components of the feeding behavior in rats.