Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice

Background & Aims: Pancreatic polypeptide (PP) is a 36-amino acid hormone p roduced by F cells within the pancreatic islets and the exocrine pancreas, The definitive function of PP in mammalian physiology remains to be determi ned, This study examined the effects of chronic overexpression of PP throug h the development of PP transgenic mice, Methods: PP transgenic mice were c reated by using mouse PP complementary DNA under the control of the cytomeg alovirus immediate early enhancer-chicken beta-actin hybrid promoter (pCAGG S expression vector). Results: A unique line of transgenic mice was created that overexpresses PP in the pancreatic islets with low levels of expressi on in other tissues including the brain, Plasma PP concentrations were more than 20 times higher than those of control littermates. However, PP overpr oduction led to postnatal lethality in half of the pups because of markedly decreased milk intake, The remaining PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared with controls, a result that was more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization w ith anti-PP antiserum reversed the phenotypic changes of transgenic animals , Conclusions: PP could be involved in feeding and body weight regulation p artly through regulation of gastric emptying.