Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Autores
Schellekens, Harriët; de Francesco, Pablo Nicolás; Kandil, Dalia; Theeuwes, Wessel F.; McCarthy, Triona; Van Oeffelen, Wesley E. P. A.; Perello, Mario; Giblin, Linda; Dinan, Timothy G.; Cryan, John F.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.
Fil: Schellekens, Harriët. University College Cork; Irlanda
Fil: de Francesco, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Kandil, Dalia. University College Cork; Irlanda
Fil: Theeuwes, Wessel F.. University College Cork; Irlanda
Fil: McCarthy, Triona. University College Cork; Irlanda
Fil: Van Oeffelen, Wesley E. P. A.. University College Cork; Irlanda
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Giblin, Linda. Teagasc Food Research Centre; Irlanda
Fil: Dinan, Timothy G.. University College Cork; Irlanda
Fil: Cryan, John F.. University College Cork; Irlanda
Materia
FOOD INTAKE
GHRELIN
GROWTH HORMONE SECRETAGOGUE RECEPTOR
LORCASERIN
SEROTONIN 2C RECEPTOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/53970
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/53970
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor InteractionSchellekens, Harriëtde Francesco, Pablo NicolásKandil, DaliaTheeuwes, Wessel F.McCarthy, TrionaVan Oeffelen, Wesley E. P. A.Perello, MarioGiblin, LindaDinan, Timothy G.Cryan, John F.FOOD INTAKEGHRELINGROWTH HORMONE SECRETAGOGUE RECEPTORLORCASERINSEROTONIN 2C RECEPTORhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.Fil: Schellekens, Harriët. University College Cork; IrlandaFil: de Francesco, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Kandil, Dalia. University College Cork; IrlandaFil: Theeuwes, Wessel F.. University College Cork; IrlandaFil: McCarthy, Triona. University College Cork; IrlandaFil: Van Oeffelen, Wesley E. P. A.. University College Cork; IrlandaFil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Giblin, Linda. Teagasc Food Research Centre; IrlandaFil: Dinan, Timothy G.. University College Cork; IrlandaFil: Cryan, John F.. University College Cork; IrlandaAmerican Chemical Society2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53970Schellekens, Harriët; de Francesco, Pablo Nicolás; Kandil, Dalia; Theeuwes, Wessel F.; McCarthy, Triona; et al.; Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction; American Chemical Society; ACS Chemical Neuroscience; 6; 7; 7-2015; 1186-11971948-7193CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/cn500318qinfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/cn500318qinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:10Zoai:ri.conicet.gov.ar:11336/53970instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:11.074CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
title Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
spellingShingle Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
Schellekens, Harriët
FOOD INTAKE
GHRELIN
GROWTH HORMONE SECRETAGOGUE RECEPTOR
LORCASERIN
SEROTONIN 2C RECEPTOR
title_short Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
title_full Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
title_fullStr Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
title_full_unstemmed Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
title_sort Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
dc.creator.none.fl_str_mv Schellekens, Harriët
de Francesco, Pablo Nicolás
Kandil, Dalia
Theeuwes, Wessel F.
McCarthy, Triona
Van Oeffelen, Wesley E. P. A.
Perello, Mario
Giblin, Linda
Dinan, Timothy G.
Cryan, John F.
author Schellekens, Harriët
author_facet Schellekens, Harriët
de Francesco, Pablo Nicolás
Kandil, Dalia
Theeuwes, Wessel F.
McCarthy, Triona
Van Oeffelen, Wesley E. P. A.
Perello, Mario
Giblin, Linda
Dinan, Timothy G.
Cryan, John F.
author_role author
author2 de Francesco, Pablo Nicolás
Kandil, Dalia
Theeuwes, Wessel F.
McCarthy, Triona
Van Oeffelen, Wesley E. P. A.
Perello, Mario
Giblin, Linda
Dinan, Timothy G.
Cryan, John F.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FOOD INTAKE
GHRELIN
GROWTH HORMONE SECRETAGOGUE RECEPTOR
LORCASERIN
SEROTONIN 2C RECEPTOR
topic FOOD INTAKE
GHRELIN
GROWTH HORMONE SECRETAGOGUE RECEPTOR
LORCASERIN
SEROTONIN 2C RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.
Fil: Schellekens, Harriët. University College Cork; Irlanda
Fil: de Francesco, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Kandil, Dalia. University College Cork; Irlanda
Fil: Theeuwes, Wessel F.. University College Cork; Irlanda
Fil: McCarthy, Triona. University College Cork; Irlanda
Fil: Van Oeffelen, Wesley E. P. A.. University College Cork; Irlanda
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Giblin, Linda. Teagasc Food Research Centre; Irlanda
Fil: Dinan, Timothy G.. University College Cork; Irlanda
Fil: Cryan, John F.. University College Cork; Irlanda
description Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/53970
Schellekens, Harriët; de Francesco, Pablo Nicolás; Kandil, Dalia; Theeuwes, Wessel F.; McCarthy, Triona; et al.; Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction; American Chemical Society; ACS Chemical Neuroscience; 6; 7; 7-2015; 1186-1197
1948-7193
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53970
identifier_str_mv Schellekens, Harriët; de Francesco, Pablo Nicolás; Kandil, Dalia; Theeuwes, Wessel F.; McCarthy, Triona; et al.; Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction; American Chemical Society; ACS Chemical Neuroscience; 6; 7; 7-2015; 1186-1197
1948-7193
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/cn500318q
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/cn500318q
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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