Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes
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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.
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Ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express GHSR, such as neurons and astrocytes.
“Hence, ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express the GHSR, such as neurons [53, 54, 57] and astrocytes [58].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [58]
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“Ultimately, the latter changes led to reduced glucose uptake, elevated glutamate uptake and the steadily rising lactate levels in the cell culture medium (Fuente-Martin et al., 2016).”
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- Authors
- Fuente-Martín, E., García-Cáceres, C., Argente-Arizón, P., Díaz, F., Granado, M., Freire-Regatillo, A., Castro-González, D., Ceballos, M. L., Frago, L. M., Dickson, S. L., Argente, J., & Chowen, J. A.
- Affiliations
- Instituto de Salud Carlos III (ES)
- University of Gothenburg (SE)
- Corresponding author
- Chowen, Julie A.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-03-30
- Volume
- 6
- Issue
- 1
- Pages
- 23673-23673
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4812252
- OpenAlex
- W2316235633
- Cited by
- 91
- References
- 67
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 12 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 5 · 2017: 15 · 2016: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Hispana (submittedVersion)
- Site cant be reached (submittedVersion, cc-by)
- Funders
- European Commission (607310)
- Vetenskapsrådet
- Ministerio de Ciencia e Innovación (BFU2011-27492, BFU 2014-51836-C2-2-R, BFU2014-51836-C2-2)
- Novo Nordisk Fonden (NNF13OC0004819, NNF12OC1016479)
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ghrelin, hypothalamic astrocytes, acylated ghrelin, des-acyl ghrelin, GLUT2, glucose uptake, glutamate transporters, glutamate uptake, glycogen metabolism, lactate transport, glutamine synthetase, lactate dehydrogenase, glycogen phosphorylase, appetite regulation, glucose metabolism
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Glucose, Hypothalamus, Male, Rats, Wistar, Mice, Knockout, Glutamic Acid, Glucose Transporter Type 2, Ghrelin, Receptors, Ghrelin
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