Central and Peripheral Administration of Secretin Inhibits Food Intake in Mice through the Activation of the Melanocortin System
Open accessAbstract
Secretin (Sct) is released into the circulation postprandially from the duodenal S-cells. The major functions of Sct originated from the gastrointestinal system are to delay gastric emptying, stimulate fluid secretion from pancreas and liver, and hence 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). These nuclei are the primary brain sites that are engaged in regulating body energy homeostasis, thus providing anatomical evidence to 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 secretin receptor-deficient (Sctr(-/-)) mice. We found that both central and peripheral administration of Sct could 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 thyrotropin-releasing hormone and melanocortin-4 receptor (Mc4r) transcripts in the PVN, and augment proopiomelanocortin, but reduces agouti-related protein mRNA expression in the Arc. Injection of Sct was able to suppress food intake in wt mice, but not in Sctr(-/-) mice, and that this effect was abolished upon pretreatment with SHU9119, an antagonist for Mc4r. In summary, our data suggest for the first time that Sct is an anorectic peptide, and that this function is mediated by the melanocortin system.
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Secretin can inhibit food intake via activation of secretin receptor in vagal sensory nerves and melanocortin signaling in the brain.
“Moreover, secretin can also inhibit food intake via the activation of secretin receptor (SctR) in vagal sensory nerves and melanocortin signaling in the brain 22, 23.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [22]
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Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition
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Structure and dynamics of the active Gs-coupled human secretin receptor
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Self-citationCD36 Senses Dietary Lipids and Regulates Lipids Homeostasis in the Intestine
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Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?
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- Authors
- Cheng, C. Y. Y., Chu, J. Y. S., & Chow, B. K. C.
- Affiliations
- University of Hong Kong (HK)
- Venue
- Neuropsychopharmacology
- Published
- 2010-10-06
- Volume
- 36
- Issue
- 2
- Pages
- 459-471
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055665
- OpenAlex
- W2011588666
- Cited by
- 98
- References
- 83
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 9
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- South Carolina Clinical and Translational Research Institute, Medical University of South Carolina
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- secretin, secretin receptor, dietary intake, melanocortin system, melanocortin-4 receptor, hypothalamus, paraventricular nucleus, arcuate nucleus, appetite regulation, anorectic peptides, thyrotropin-releasing hormone, proopiomelanocortin, agouti-related protein, SHU9119, energy homeostasis
- MeSH terms
- Animals, Appetite Depressants, Appetite Regulation, Arcuate Nucleus of Hypothalamus, Feeding Behavior, Hypothalamus, Injections, Intraperitoneal, Injections, Intraventricular, Male, Neurons, Pro-Opiomelanocortin, Random Allocation, Receptors, Gastrointestinal Hormone, Secretin, Down-Regulation, Mice, Knockout, Receptors, G-Protein-Coupled, Mice
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