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Title: Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex
Author: Mir Bonnín, Joan Francesc
Zagmutt Caroxa, Sebastián
Lichtenstein, Mathieu P.
García Villoria, Judit
Weber Blattes, Minéia
Gracia, Ana
Fabriàs Domingo, Gemma
Casas Brugulat, Josefina
López, Miguel
Casals i Farré, Núria
Ribes Rubió, Maria Antònia
Suñol, Cristina
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Keywords: Metabolisme dels lípids
Àcids grassos
Hormones peptídiques
Escorça cerebral
Lipid metabolism
Fatty acids
Peptide hormones
Cerebral cortex
Issue Date: 2-Feb-2018
Publisher: Humana Press.
Abstract: Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system. Keywords: Ghrelin, GABA, Fatty acid oxidation, CPT1A, Cortical neurons
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It is part of: Molecular Neurobiology, 2018
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ISSN: 0893-7648
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Publicacions de projectes de recerca finançats per la UE

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