Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice

Autores
Wasinski, Frederick; Barrile, Franco; Pedroso, João A. B.; Quaresma, Paula G. F.; Dos Santos, Willian O.; List, Edward O.; Kopchick, John J.; Perelló, Mario; Donato, Jose
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.
Fil: Wasinski, Frederick. Universidade de Sao Paulo; Brasil
Fil: Barrile, Franco. 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: Pedroso, João A. B.. Universidade de Sao Paulo; Brasil
Fil: Quaresma, Paula G. F.. Universidade de Sao Paulo; Brasil
Fil: Dos Santos, Willian O.. Universidade de Sao Paulo; Brasil
Fil: List, Edward O.. Ohio University; Estados Unidos
Fil: Kopchick, John J.. Ohio University; Estados Unidos
Fil: Perelló, Mario. Multidisciplinary Institute Of Cell Biology; Argentina
Fil: Donato, Jose. Universidade de Sao Paulo; Brasil
Materia
CYTOKINES
ENERGY BALANCE
GROWTH HORMONE RECEPTOR
HYPOTHALAMUS
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:11336/181066
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/181066
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male MiceWasinski, FrederickBarrile, FrancoPedroso, João A. B.Quaresma, Paula G. F.Dos Santos, Willian O.List, Edward O.Kopchick, John J.Perelló, MarioDonato, JoseCYTOKINESENERGY BALANCEGROWTH HORMONE RECEPTORHYPOTHALAMUShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.Fil: Wasinski, Frederick. Universidade de Sao Paulo; BrasilFil: Barrile, Franco. 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: Pedroso, João A. B.. Universidade de Sao Paulo; BrasilFil: Quaresma, Paula G. F.. Universidade de Sao Paulo; BrasilFil: Dos Santos, Willian O.. Universidade de Sao Paulo; BrasilFil: List, Edward O.. Ohio University; Estados UnidosFil: Kopchick, John J.. Ohio University; Estados UnidosFil: Perelló, Mario. Multidisciplinary Institute Of Cell Biology; ArgentinaFil: Donato, Jose. Universidade de Sao Paulo; BrasilEndocrine Society2021-07info: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/11336/181066Wasinski, Frederick; Barrile, Franco; Pedroso, João A. B.; Quaresma, Paula G. F.; Dos Santos, Willian O.; et al.; Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice; Endocrine Society; Endocrinology; 162; 7; 7-2021; 1-150013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/endocr/bqab097info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:11Zoai:ri.conicet.gov.ar:11336/181066instacron: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 09:46:12.785CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
title Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
spellingShingle Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
Wasinski, Frederick
CYTOKINES
ENERGY BALANCE
GROWTH HORMONE RECEPTOR
HYPOTHALAMUS
title_short Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
title_full Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
title_fullStr Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
title_full_unstemmed Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
title_sort Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice
dc.creator.none.fl_str_mv Wasinski, Frederick
Barrile, Franco
Pedroso, João A. B.
Quaresma, Paula G. F.
Dos Santos, Willian O.
List, Edward O.
Kopchick, John J.
Perelló, Mario
Donato, Jose
author Wasinski, Frederick
author_facet Wasinski, Frederick
Barrile, Franco
Pedroso, João A. B.
Quaresma, Paula G. F.
Dos Santos, Willian O.
List, Edward O.
Kopchick, John J.
Perelló, Mario
Donato, Jose
author_role author
author2 Barrile, Franco
Pedroso, João A. B.
Quaresma, Paula G. F.
Dos Santos, Willian O.
List, Edward O.
Kopchick, John J.
Perelló, Mario
Donato, Jose
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CYTOKINES
ENERGY BALANCE
GROWTH HORMONE RECEPTOR
HYPOTHALAMUS
topic CYTOKINES
ENERGY BALANCE
GROWTH HORMONE RECEPTOR
HYPOTHALAMUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.
Fil: Wasinski, Frederick. Universidade de Sao Paulo; Brasil
Fil: Barrile, Franco. 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: Pedroso, João A. B.. Universidade de Sao Paulo; Brasil
Fil: Quaresma, Paula G. F.. Universidade de Sao Paulo; Brasil
Fil: Dos Santos, Willian O.. Universidade de Sao Paulo; Brasil
Fil: List, Edward O.. Ohio University; Estados Unidos
Fil: Kopchick, John J.. Ohio University; Estados Unidos
Fil: Perelló, Mario. Multidisciplinary Institute Of Cell Biology; Argentina
Fil: Donato, Jose. Universidade de Sao Paulo; Brasil
description Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.
publishDate 2021
dc.date.none.fl_str_mv 2021-07
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/11336/181066
Wasinski, Frederick; Barrile, Franco; Pedroso, João A. B.; Quaresma, Paula G. F.; Dos Santos, Willian O.; et al.; Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice; Endocrine Society; Endocrinology; 162; 7; 7-2021; 1-15
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181066
identifier_str_mv Wasinski, Frederick; Barrile, Franco; Pedroso, João A. B.; Quaresma, Paula G. F.; Dos Santos, Willian O.; et al.; Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice; Endocrine Society; Endocrinology; 162; 7; 7-2021; 1-15
0013-7227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1210/endocr/bqab097
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 Endocrine Society
publisher.none.fl_str_mv Endocrine 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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