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...

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Main Authors:	Fuente-Martín, Esther, García-Cáceres, Cristina, Argente-Arizón, Pilar, Díaz, Francisca, Granado, Miriam, Freire-Regatillo, Alejandra, Castro-González, David, Ceballos, María L., Frago, Laura M., Dickson, Suzanne L., Argente, Jesús, Chowen, Julie A.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812252/

id	pubmed-4812252
recordtype	oai_dc
spelling	pubmed-48122522016-04-04 Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago, Laura M. Dickson, Suzanne L. Argente, Jesús Chowen, Julie A. Article 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. Nature Publishing Group 2016-03-30 /pmc/articles/PMC4812252/ /pubmed/27026049 http://dx.doi.org/10.1038/srep23673 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago, Laura M. Dickson, Suzanne L. Argente, Jesús Chowen, Julie A.
spellingShingle	Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago, Laura M. Dickson, Suzanne L. Argente, Jesús Chowen, Julie A. Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes
author_facet	Fuente-Martín, Esther García-Cáceres, Cristina Argente-Arizón, Pilar Díaz, Francisca Granado, Miriam Freire-Regatillo, Alejandra Castro-González, David Ceballos, María L. Frago, Laura M. Dickson, Suzanne L. Argente, Jesús Chowen, Julie A.
author_sort	Fuente-Martín, Esther
title	Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes
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
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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812252/
_version_	1613559326076567552

Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes

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