The role of secretin in appetite control

Abstract

Multiple gut hormones are involved in the regulation of food intake. Secretin

(SCT), a classical gut hormone, is released into the circulation from the duodenal

S-cells when acidic chyme enters the duodenum and performs the major functions

of delaying gastric emptying, stimulating fluid secretion from pancreas and liver

to optimize the digestion process. In recent years, SCT and its receptor (SCTR)

have been identified in discrete nuclei of the hypothalamus, including the

paraventricular nucleus (PVN) and the arcuate nucleus (Arc). The occurrence of

SCT and SCTR in the brain regions that are engaged in regulating body energy

homeostasis and the release pattern of SCT after meals support a functional role of

SCT in appetite control. In this study, the effect of SCT on feeding behavior was

investigated using wild-type (wt), SCT?/?, and SCT receptor-deficient (SCTR?/?)

mice. We found that both central and peripheral administration of SCT could

reduce food intake in wt but not in SCTR?/?mice. SCT induce Fos expression in

the PVN and Arc, suggesting the activation of hypothalamic feeding centers by

this peptide. Consistent with this notion, SCT was found to increase

proopiomelanocortin (POMC), but reduce agouti-related protein (AgRP)

transcripts in the Arc, and augment thyrotropin-releasing hormone (TRH) and

melanocortin-4 receptor (MC4R) mRNA expression in the PVN. In addition,

pretreatment with SHU9119, an antagonist for MC4R, abolished the anorexia

induced by SCT, suggesting that SCT may inhibit food intake via a

melanocortin-dependent pathway. Gut hormones signals the brain to modulate the

feeding behavior via the vagal afferent nerve, bloodstream or both. Here we

showed that peripheral SCT-induced anorexia was attenuated in mice with

subdiaphragmatic vagotomy, capsaicin treatment and bilateral midbrain

transections. In summary, our data identify peripheral SCT as an anorectic peptide

exerting its action via the melanocortin system and the vagal afferent contributes a

major route in mediating the inhibitory effect of peripheral SCT on food intake.

The present findings advance our understanding of the role of gut hormones in the

regulation of appetite.