Central administration of secretin suppresses food intake in mice

Session 5: Endocrine System and Metabolism: no. O13This journal issue entitled: Special Issue: VIP, PACAP and Related PeptidesSecretin is released into the circulation postprandially from the duodenal S cells. The major functions of secretin originated from the gastrointestinal system are to delay gastric emptying, stimulate fluid secretion from pancreas and liver, and hence, optimize the digestion process. In our laboratory, secretin and its receptor have recently been identified in mice hypothalamus where it has long been considered as an important center in the regulation of energy homeostasis. By altering the rate at which nutrients are delivered to compartments of the alimentary canal and being highly expressed in hypothalamic nuclei, secretin could therefore be involved in appetite control. In this study, the functional role of secretin on feeding regulation was investigated. Intracerebroventricular (ICV) administration of secretin (0.15 nmol) into the lateral ventricle was found to suppress food intake in both fasted mice or ad libitum fed wild-type mice but not in fasted mice or ad libitum fed secretin receptor knockout mice (SCTR−/−). In addition, central administration of secretin could induce Fos expression in hypothalamic nuclei, including the paraventricular nucleus (PVN) and the arcuate nucleus (Arc). Consistent with these findings, ICV-secretin could also change expressions of appetite control proteins in various hypothalamic nuclei. It could activate proopiomelanocortin (POMC), reduce agoutirelated protein (AgRP) mRNA expression in the Arc, and increase thyrotropin-releasing hormone (TRH) transcripts in the PVN, while these effects of ICV-secretin were not found in SCTR−/−. Altogether, our data suggest that secretin, via its receptor, could inhibit food intake and that this action could be mediated by changing the expressions of POMC and AgRP in the Arc and TRH in the PVN