Vagal Afferent Mediates the Anorectic Effect of Peripheral Secretin

Abstract

Secretin (SCT) is a classical peptide hormone that is synthesized and released from the gastrointestinal tract after a meal. We have previously shown that it acts both as a central and peripheral anorectic peptide, and that its central effect is mediated via melanocortin system. As peripheral satiety signals from the gastrointestinal tract can be sent to the brain via the vagal afferent or by crossing the blood-brain barrier (BBB), we therefore sought to investigate the pathway by which peripheral SCT reduces appetite in this study. It is found that bilateral subdiaphragmatic vagotomy and treatment of capsaicin, an excitotoxin for primary afferent neurons, could both block the anorectic effect of peripherally injected SCT. These treatments are found to be capable of blunting i.p. SCT-induced Fos activation in pro-opiomelanocortin (POMC) neurons within the hypothalamic Arcuate Nucleus (Arc). Moreover, we have also found that bilateral midbrain transaction could block feeding reduction by peripheral SCT. Taken together, we conclude that the satiety signals of peripheral SCT released from the gastrointestinal tract are sent via the vagus nerves to the brainstem and subsequently Arc, where it controls central expression of other regulatory peptides to regulate food intake.

Oxytocin – The Sweet Hormone?

“…Gastric distension also activates magnocellular oxytocin neurons, probably also via activation of NTS neurons, though whether these are the same neurons as are activated by CCK is not known [39]. Both oxytocin and vasopressin neurons in the SON are also activated by systemic administration of secretin [40], a hormone secreted from the duodenum in response to food intake which regulates gastric secretion and emptying, and this again is mediated by a vagal projection to the NTS [41].…”

Central Control of Feeding Behavior by the Secretin, PACAP, and Glucagon Family of Peptides

“…and i.p. SCT ( 39 , 46 ). In addition, it has been reported that central and peripheral SCT increased melanocortin-4 receptor (MC4R) mRNA in the PVN, and administration of MC4R antagonist, SHU9119, in the PVN reduced the anorectic effect of central and peripheral SCT, indicating the involvement of melanocortin system ( 39 , 46 ).…”

“…SCT ( 39 , 46 ). In addition, it has been reported that central and peripheral SCT increased melanocortin-4 receptor (MC4R) mRNA in the PVN, and administration of MC4R antagonist, SHU9119, in the PVN reduced the anorectic effect of central and peripheral SCT, indicating the involvement of melanocortin system ( 39 , 46 ). We previously showed that K + -induced depolarization of hypothalamic explants released SCT endogenously through voltage-gated sodium and calcium channels, suggesting that this endogenous SCT could function as a neurotransmitter in the region ( 34 , 35 ).…”

Role of Secretin Peptide Family and their Receptors in the Hypothalamic Control of Energy Homeostasis

“…I.p.-SCT stimulates c-Fos expression in area prostema (AP) and NTS of the brainstem as well as ARC and PVN of the hypothalamus, and this eff ect of SCT was blocked by subdiaphragmatic vagotomy [ 34 , 38 ] . Additionally, a more recent report from our laboratory shows that subdiaphragmatic vagotomy also abolishes the anorectic eff ect of i.p.-SCT [ 39 ] . Although SCT has been shown to cross the bloodbrain barrier (BBB) [ 40 ] , these studies therefore indicate that circulating SCT does not cross the BBB to exert its anorectic eff ect.…”