Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice

Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain...

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Autores principales: Fernández, Gimena, Cabral, Agustina Soledad, Andreoli, Maria Florencia, Labarthe, Alexandra, M'Kadmi, Céline, Ramos, Jorge G., Marie, Jacky, Fehrentz, Jean-Alain, Epelbaum, Jacques, Tolle, Virginie, Perelló, Mario Carlos
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Biología
Ghrelin Receptor
Growth hormone secretagogue receptor
Fasting
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/137540
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-137540
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ghrelin Receptor
Growth hormone secretagogue receptor
Fasting
spellingShingle Biología
Ghrelin Receptor
Growth hormone secretagogue receptor
Fasting
Fernández, Gimena
Cabral, Agustina Soledad
Andreoli, Maria Florencia
Labarthe, Alexandra
M'Kadmi, Céline
Ramos, Jorge G.
Marie, Jacky
Fehrentz, Jean-Alain
Epelbaum, Jacques
Tolle, Virginie
Perelló, Mario Carlos
Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
topic_facet Biología
Ghrelin Receptor
Growth hormone secretagogue receptor
Fasting
description Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain. As GHSR gene expression in the hypothalamus is known to increase in fasting conditions, we tested the hypothesis that constitutive GHSR activity at the hypothalamic level drives the fasting-induced hyperphagia. We found that refed wild-type (WT) mice displayed a robust hyperphagia that continued for 5 days after refeeding and changed their food intake daily pattern. Fasted WT mice showed an increase in plasma ghrelin levels, as well as in GHSR expression levels and ghrelin binding sites in the hypothalamic arcuate nucleus. When fasting-refeeding responses were evaluated in ghrelin- or GHSR-deficient mice, only the latter displayed an ∼15% smaller hyperphagia, compared with WT mice. Finally, fasting-induced hyperphagia of WT mice was significantly smaller in mice centrally treated with the GHSR inverse agonist K-(D-1-Nal)-FwLL-NH2, compared with mice treated with vehicle, whereas it was unaffected in mice centrally treated with the GHSR antagonists D-Lys3-growth hormone-releasing peptide 6 or JMV2959. Taken together, genetic models and pharmacological results support the notion that constitutive GHSR activity modulates the magnitude of the compensatory hyperphagia triggered by fasting. Thus, the hypothalamic GHSR signaling system could affect the set point of daily food intake, independently of plasma ghrelin levels, in situations of negative energy balance.
format Articulo
Articulo
author Fernández, Gimena
Cabral, Agustina Soledad
Andreoli, Maria Florencia
Labarthe, Alexandra
M'Kadmi, Céline
Ramos, Jorge G.
Marie, Jacky
Fehrentz, Jean-Alain
Epelbaum, Jacques
Tolle, Virginie
Perelló, Mario Carlos
author_facet Fernández, Gimena
Cabral, Agustina Soledad
Andreoli, Maria Florencia
Labarthe, Alexandra
M'Kadmi, Céline
Ramos, Jorge G.
Marie, Jacky
Fehrentz, Jean-Alain
Epelbaum, Jacques
Tolle, Virginie
Perelló, Mario Carlos
author_sort Fernández, Gimena
title Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
title_short Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
title_full Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
title_fullStr Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
title_full_unstemmed Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice
title_sort evidence supporting a role for constitutive ghrelin receptor signaling in fasting-induced hyperphagia in male mice
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/137540
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