title: Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus.
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.
authors.affiliation: Department of Anatomy, Medical School, University of Pécs, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Füredi
authors.affiliation: Department of Anatomy, Medical School, University of Pécs, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Nagy
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mikó
authors.affiliation: Department of Medical Biology, Medical School, University of Pécs, Szigeti u.12, Pécs, H-7624, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Berta
authors.affiliation: Department of Anatomy, Medical Centre, Radboud University Nijmegen, Geert Grooteplein Noord 21 (route 109), 6500HB Nijmegen, The Netherlands.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kozicz
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pétervári
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Balaskó
authors.affiliation: Department of Anatomy, Medical School, University of Pécs, Hungary. Electronic address: balazs.b.gaszner@aok.pte.hu.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gaszner
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004333:Drug Administration Routes; D004435:Eating / Q000187:drug effects; D065839:Edinger-Westphal Nucleus / Q000166:cytology*; D005215:Fasting; D006706:Homeostasis / Q000187:drug effects*; D008024:Ligands; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D054832:Urocortins / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; C116098:HS 024; D008024:Ligands; D016761:Oncogene Proteins v-fos; D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D054832:Urocortins; D000521:alpha-MSH
keywords: Energy homeostasis; Feeding; Melanocortin system; Starvation; Stress