Melanocortin-4 receptor expression in a vago-vagal circuitry involved in postprandial functions

Laurent Gautron, Charlotte Lee, Hisayuki Funahashi, Jeffrey Friedman, Syann Lee, Joel Elmquist

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Vagal afferents regulate energy balance by providing a link between the brain and postprandial signals originating from the gut. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the nodose ganglion, where the cell bodies of vagal sensory afferents reside. By using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found GFP expression in approximately one-third of nodose ganglion neurons. By using immunohistochemistry combined with in situ hybridization, we also demonstrated that ∼20% of GFP-positive neurons coexpressed cholecystokinin receptor A. In addition, we found that the GFP is transported to peripheral tissues by both vagal sensory afferents and motor efferents, which allowed us to assess the sites innervated by MC4R-GFP neurons. GFP-positive efferents that coexpressed choline acetyltransferase specifically terminated in the hepatic artery and the myenteric plexus of the stomach and duodenum. In contrast, GFP-positive afferents that did not express cholinergic or sympathetic markers terminated in the submucosal plexus and mucosa of the duodenum. Retrograde tracing experiments confirmed the innervation of the duodenum by GFP-positive neurons located in the nodose ganglion. Our findings support the hypothesis that MC4R signaling in vagal afferents may modulate the activity of fibers sensitive to satiety signals such as cholecystokinin, and that MC4R signaling in vagal efferents may contribute to the control of the liver and gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)6-24
Number of pages19
JournalJournal of Comparative Neurology
Volume518
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Receptor, Melanocortin, Type 4
Green Fluorescent Proteins
Nodose Ganglion
Duodenum
Neurons
Tetragastrin
Cholecystokinin A Receptor
Submucous Plexus
Myenteric Plexus
Choline O-Acetyltransferase
Hepatic Artery
Cholinergic Agents
In Situ Hybridization
Gastrointestinal Tract
Stomach
Mucous Membrane
Immunohistochemistry

Keywords

  • Cholecystokinin
  • Green fluorescent protein
  • Satiety
  • Vagus nerve

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Melanocortin-4 receptor expression in a vago-vagal circuitry involved in postprandial functions. / Gautron, Laurent; Lee, Charlotte; Funahashi, Hisayuki; Friedman, Jeffrey; Lee, Syann; Elmquist, Joel.

In: Journal of Comparative Neurology, Vol. 518, No. 1, 01.01.2010, p. 6-24.

Research output: Contribution to journalArticle

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