GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function.
FGF-21
GLP-1
astrocytes
energy homeostasis
glucose metabolism
hepatic glucose production
mitochondria
obesity
stress response
ß-oxidation
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
03
05
2019
revised:
09
12
2019
accepted:
02
05
2020
pubmed:
21
5
2020
medline:
10
11
2021
entrez:
21
5
2020
Statut:
ppublish
Résumé
Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes β-oxidation in cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion in glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs astrocyte mitochondrial integrity and activates an integrated stress response with enhanced fibroblast growth factor (FGF)21 production and increased brain glucose uptake. Accordingly, central neutralization of FGF21 or astrocyte-specific FGF21 inactivation abrogates the improvements in glucose tolerance and learning in mice lacking GLP-1R expression in astrocytes. Collectively, these experiments reveal a role for astrocyte GLP-1R signaling in maintaining mitochondrial integrity, and lack of GLP-1R signaling mounts an adaptive stress response resulting in an improvement of systemic glucose homeostasis and memory formation.
Identifiants
pubmed: 32433922
pii: S1550-4131(20)30240-0
doi: 10.1016/j.cmet.2020.05.001
pmc: PMC7272126
pii:
doi:
Substances chimiques
Fatty Acids
0
Glucagon-Like Peptide-1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1189-1205.e13Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK111178
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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