title: Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes.
abstract: 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.
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Fuente-Martín
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Cáceres
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Argente-Arizón
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Díaz
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Granado
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Freire-Regatillo
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Castro-González
authors.affiliation: Instituto Cajal, Dept. of Cellular, Molecular and Developmental Neurobiology, and CIBERNED, CSIC, Madrid, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Ceballos
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Frago
authors.affiliation: Dept. Physiology/Endocrine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Dickson
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, University Autónoma of Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D054439:Ghrelin / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D008297:Male; D018345:Mice, Knockout; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D005947:Glucose; D051273:Glucose Transporter Type 2; D018698:Glutamic Acid; D054440:Receptors, Ghrelin; C000592182:Ghsr protein, Mouse; C495682:Slc2a2 protein, mouse