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Cited by 179Neuropeptides and Animal PhysiologyRegulation of Appetite and ObesityPancreatic function and diabetes

The Melanocortin-4 Receptor Is Expressed in Enteroendocrine L Cells and Regulates the Release of Peptide YY and Glucagon-like Peptide 1 In Vivo

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Panaro, Brandon L., Tough, Iain R., Engelstoft, Maja S., Matthews, Robert T., Digby, Gregory J., Møller, Cathrine L., Svendsen, Berit, Gribble, Fiona +6 more·2014·Cell Metabolism
DOI 10.1016/j.cmet.2014.10.004PMC PMC4255280
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Abstract

The melanocortin-4 receptor (MC4R) is expressed in the brainstem and vagal afferent nerves and regulates a number of aspects of gastrointestinal function. Here we show that the receptor is also diffusely expressed in cells of the gastrointestinal system, from stomach to descending colon. Furthermore, MC4R is the second most highly enriched GPCR in peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) expressing enteroendocrine L cells. When vectorial ion transport is measured across mouse or human intestinal mucosa, administration of α-MSH induces a MC4R-specific PYY-dependent antisecretory response consistent with a role for the MC4R in paracrine inhibition of electrolyte secretion. Finally, MC4R-dependent acute PYY and GLP-1 release from L cells can be stimulated in vivo by intraperitoneal (i.p.) administration of melanocortin peptides to mice. This suggests physiological significance for MC4R in L cells and indicates a previously unrecognized peripheral role for the MC4R, complementing vagal and central receptor functions.

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  • Peripheral α-MSH triggers release of PYY and GLP-1 from EEC L cells in the gut via activation of the melanocortin 4 receptor.

    “peripheral α-MSH was shown to trigger the release of PYY and GLP-1 from EEC L cells in the gut via activation of the melanocortin 4 receptor (Panaro et al., 2014).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Panaro et al., 2014

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References 42 · Cited by 179

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Authors
Panaro, B. L., Tough, I. R., Engelstoft, M. S., Matthews, R. T., Digby, G. J., Møller, C. L., Svendsen, B., Gribble, F., Reimann, F., Holst, J. J., Holst, B., Schwartz, T. W., Cox, H. M., & Cone, R. D.
Affiliations
  • Vanderbilt University (US)
  • King's College London (GB)
  • University of Copenhagen (DK)
  • University of Cambridge (GB)
Corresponding author
Cone, Roger D.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2014-12
Volume
20
Issue
6
Pages
1018-1029
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2014.10.004
PMC
PMC4255280
OpenAlex
W2161888764
Cited by
179
References
42
Citations by year
2026: 13 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 10 · 2021: 21 · 2020: 14 · 2019: 13 · 2018: 11 · 2017: 16 · 2016: 21 · 2015: 18 · 2014: 1
FWCI
8.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Figshare (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • National Institutes of Health (R24DK096527, RO1DK070332, WT084210/Z/07/Z, WT088357/Z/09/Z)
  • Novo Nordisk Fonden
  • Novo Nordisk Foundation Center for Basic Metabolic Research
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
melanocortin-4 receptor, enteroendocrine L cells, peptide YY, glucagon-like peptide-1, alpha-melanocyte-stimulating hormone, intestinal ion transport, gut-brain signaling, melanocortin peptides
MeSH terms
Acids, Heterocyclic, Animals, Colon, Humans, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Oxadiazoles, Peptides, Cyclic, Enteroendocrine Cells, Peptide YY, Receptor, Melanocortin, Type 4, Mice, Glucagon-Like Peptide 1

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