Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus

Nóra Füredi, Ákos Nagy, Alexandra Mikó, Gergely Berta, Tamás Kozicz, Erika Pétervári, M. Balaskó, B. Gaszner

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The role of the urocortin 1 (Ucn1) expressing centrally projecting Edinger-Westphal (EWcp) nucleus in energy homeostasis and stress adaptation response has previously been investigated. Morphological and functional studies have proven that orexigenic and anorexigenic peptidergic afferents and receptors for endocrine messengers involved in the energy homeostasis are found in the EWcp. The central role of the hypothalamic melanocortin system in energy homeostasis is well known, however, no data have been published so far on possible crosstalk between melanocortins and EWcp-Ucn1. First, we hypothesized that members of the melanocortin system [i.e. alpha-melanocyte stimulating hormone (alpha-MSH), agouti-related peptide (AgRP), melanocortin 4 receptor (MC4R)] would be expressed in the EWcp. Second, we put forward, that alpha-MSH and AgRP contents as well as neuronal activity and Ucn1 peptide content of the EWcp would be affected by fasting. Third, we assumed that the intra-EWcp injections of exogenous MC4R agonists and antagonist would cause food intake-related and metabolic changes. Ucn1 neurons were found to carry MC4Rs, and they were contacted both by alpha-MSH and AgRP immunoreactive nerve fibers in the rat. The alpha-MSH immunosignal was reduced, while that of AgRP was increased upon starvation. These were associated with the elevation of FosB and Ucn1 expression. The intra-EWcp administration of MC4R blocker (i.e. HS024) had a similar, but enhanced effect on FosB and Ucn1. Furthermore, alpha-MSH injected into the EWcp had anorexigenic effect, increased oxygen consumption and caused peripheral vasodilation. We conclude that the melanocortin system influences the EWcp that contributes to energy-homeostasis.

Original languageEnglish
Pages (from-to)26-37
Number of pages12
JournalNeuropharmacology
Volume118
DOIs
Publication statusPublished - May 15 2017

Fingerprint

Urocortins
Receptor, Melanocortin, Type 4
alpha-MSH
Melanocortins
Homeostasis
Ligands
Neurons
Peptides
Starvation
Nerve Fibers
Vasodilation
Oxygen Consumption
Edinger-Westphal Nucleus
Fasting
Eating
Injections
Dasyproctidae

Keywords

  • Energy homeostasis
  • Feeding
  • Melanocortin system
  • Starvation
  • Stress

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus. / Füredi, Nóra; Nagy, Ákos; Mikó, Alexandra; Berta, Gergely; Kozicz, Tamás; Pétervári, Erika; Balaskó, M.; Gaszner, B.

In: Neuropharmacology, Vol. 118, 15.05.2017, p. 26-37.

Research output: Contribution to journalArticle

Füredi, Nóra ; Nagy, Ákos ; Mikó, Alexandra ; Berta, Gergely ; Kozicz, Tamás ; Pétervári, Erika ; Balaskó, M. ; Gaszner, B. / Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus. In: Neuropharmacology. 2017 ; Vol. 118. pp. 26-37.
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AU - Berta, Gergely

AU - Kozicz, Tamás

AU - Pétervári, Erika

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