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GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution

Migrenne, Stephanie
Skytt, Dorte M
Pajecka, Kamilla
Martin-Del-Rio, Rafael
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Published in Cell Reports. 2015, vol. 13, no. 2, p. 365-375
Abstract Glucose, the main energy substrate used in the CNS, is continuously supplied by the periphery. Glutamate, the major excitatory neurotransmitter, is foreseen as a complementary energy contributor in the brain. In particular, astrocytes actively take up glutamate and may use it through oxidative glutamate dehydrogenase (GDH) activity. Here, we investigated the significance of glutamate as energy substrate for the brain. Upon glutamate exposure, astrocytes generated ATP in a GDH-dependent way. The observed lack of glutamate oxidation in brain-specific GDH null CnsGlud1(-/-) mice resulted in a central energy-deprivation state with increased ADP/ATP ratios and phospho-AMPK in the hypothalamus. This induced changes in the autonomous nervous system balance, with increased sympathetic activity promoting hepatic glucose production and mobilization of substrates reshaping peripheral energy stores. Our data reveal the importance of glutamate as necessary energy substrate for the brain and the role of central GDH in the regulation of whole-body energy homeostasis.
PMID: 26440896
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Article (Published version) (2.2 MB) - public document Free access
Research group Mitochondries et sécrétion d'insuline (671)
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KARACA EMRE, Melis et al. GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution. In: Cell Reports, 2015, vol. 13, n° 2, p. 365-375. doi: 10.1016/j.celrep.2015.09.003 https://archive-ouverte.unige.ch/unige:77866

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Deposited on : 2015-11-30

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