Timper, Katharina, del Rio-Martin, Almudena, Cremer, Anna Lena, Bremser, Stephan, Alber, Jens, Giavalisco, Patrick, Varela, Luis ORCID: 0000-0001-7794-7241, Heilinger, Christian, Nolte, Hendrik, Trifunovic, Aleksandra, Horvath, Tamas L., Kloppenburg, Peter, Backes, Heiko and Bruening, Jens C. (2020). GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function. Cell Metab., 31 (6). S. 1189 - 1219. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

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 beta-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Timper, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
del Rio-Martin, AlmudenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cremer, Anna LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bremser, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alber, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giavalisco, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varela, LuisUNSPECIFIEDorcid.org/0000-0001-7794-7241UNSPECIFIED
Heilinger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horvath, Tamas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Backes, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-330745
DOI: 10.1016/j.cmet.2020.05.001
Journal or Publication Title: Cell Metab.
Volume: 31
Number: 6
Page Range: S. 1189 - 1219
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GLUCAGON-LIKE PEPTIDE-1; GROWTH-FACTOR 21; INTEGRATED STRESS-RESPONSE; BRAIN GLUCOSE-UPTAKE; NIGRA PARS COMPACTA; SUBSTANTIA-NIGRA; INSULIN SENSITIVITY; ENERGY-EXPENDITURE; PPAR-ALPHA; RAT-BRAINMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33074

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