Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes
Hypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/677858 |
| Acceso en línea: | http://hdl.handle.net/10486/677858 https://dx.doi.org/10.1038/srep23673 |
| Access Level: | acceso abierto |
| Palabra clave: | Insulin Glucose Ghrelin 1A (GHSR-1A) GLUT2 Signals/nutrients Medicina |
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Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytesFuente-Martín, EstherGarcía-Cáceres, CristinaArgente-Arizón, PilarDíaz, FranciscaGranado García, MiriamFreire-Regatillo, AlejandraCastro-González, DavidCeballos, María L.Frago Fernández, Laura MaríaDickson, Suzanne L.Argente Oliver, JesúsChowen, Julie AnnInsulinGlucoseGhrelin1A (GHSR-1A)GLUT2Signals/nutrientsMedicinaHypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We have used both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl-ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT) 2 levels and glucose uptake by these glial cells. Glutamine synthetase and lactate dehydrogenase decrease, while glycogen phosphorylase and lactate transporters increase in response to acyl-ghrelin, suggesting a change in glutamate and glucose metabolism, as well as glycogen storage by astrocytes. These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out mice do not change glutamate transporter or GLUT2 levels in response to acyl-ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic actions through modulation of hypothalamic astrocytes and that this effect could involve astrocyte mediated changes in local glucose and glutamate metabolism that alter the signals/nutrients reaching neighboring neurons.This work was funded by grants from Fondo de Investigación Sanitaria (PI100747; PI1302195), Ministerio de Ciencia e Innovación (BFU2011–27492; BFU2014-51836-C2-2-R) and Fondos FEDER, Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, and Fundación de Endocrinología y Nutrición. SD was funded by the Swedish Research Council (Vetenskapsrådet grant 2012– 1758), Läkarutbildningsavtalet Göteborg grant at Sahlgrenska Hospital (ALFGBG-138741, The European Union Seventh Framework Programme under Grant Agreement 607310, Nudge-it)Nature Publishing GroupDepartamento de FisiologíaDepartamento de MedicinaDepartamento de PediatríaFacultad de MedicinaInstituto de Investigación del Hospital de La Princesa (IP)20162016-03-30research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/677858https://dx.doi.org/10.1038/srep23673reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6778582026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| title |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| spellingShingle |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes Fuente-Martín, Esther Insulin Glucose Ghrelin 1A (GHSR-1A) GLUT2 Signals/nutrients Medicina |
| title_short |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| title_full |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| title_fullStr |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| title_full_unstemmed |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| title_sort |
Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes |
| dc.creator.none.fl_str_mv |
Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado García, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago Fernández, Laura María Dickson, Suzanne L. Argente Oliver, Jesús Chowen, Julie Ann |
| author |
Fuente-Martín, Esther |
| author_facet |
Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado García, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago Fernández, Laura María Dickson, Suzanne L. Argente Oliver, Jesús Chowen, Julie Ann |
| author_role |
author |
| author2 |
García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado García, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago Fernández, Laura María Dickson, Suzanne L. Argente Oliver, Jesús Chowen, Julie Ann |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Fisiología Departamento de Medicina Departamento de Pediatría Facultad de Medicina Instituto de Investigación del Hospital de La Princesa (IP) |
| dc.subject.none.fl_str_mv |
Insulin Glucose Ghrelin 1A (GHSR-1A) GLUT2 Signals/nutrients Medicina |
| topic |
Insulin Glucose Ghrelin 1A (GHSR-1A) GLUT2 Signals/nutrients Medicina |
| description |
Hypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We have used both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl-ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT) 2 levels and glucose uptake by these glial cells. Glutamine synthetase and lactate dehydrogenase decrease, while glycogen phosphorylase and lactate transporters increase in response to acyl-ghrelin, suggesting a change in glutamate and glucose metabolism, as well as glycogen storage by astrocytes. These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out mice do not change glutamate transporter or GLUT2 levels in response to acyl-ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic actions through modulation of hypothalamic astrocytes and that this effect could involve astrocyte mediated changes in local glucose and glutamate metabolism that alter the signals/nutrients reaching neighboring neurons. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2016-03-30 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/677858 https://dx.doi.org/10.1038/srep23673 |
| url |
http://hdl.handle.net/10486/677858 https://dx.doi.org/10.1038/srep23673 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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