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. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/174475 |
| Date | January 2011 |
| Creators | Cheng, Yuen-yee., 鄭婉兒. |
| Contributors | Chow, BKC |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47752956 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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