Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex

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To access the full text documents, please follow this link: http://hdl.handle.net/20.500.12328/1589

dc.contributor.author	Mir, Joan Francesc
dc.contributor.author	Zagmutt, Sebastián
dc.contributor.author	Lichtenstein, Mathieu P.
dc.contributor.author	García-Villoria, Judit
dc.contributor.author	Weber, Minéia
dc.contributor.author	Gracia, Ana
dc.contributor.author	Fabriàs, Gemma
dc.contributor.author	Casas, Josefina
dc.contributor.author	López, Miguel
dc.contributor.author	Casals i Farré, Núria
dc.contributor.author	Ribes, Antònia
dc.contributor.author	Suñol, Cristina
dc.contributor.author	Herrero Rodríguez, Laura
dc.contributor.author	Serra, Dolors
dc.date	2020-06-18T18:30:41Z
dc.date	2020-06-18T18:30:41Z
dc.date	2018
dc.identifier	Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P. [et al.]. Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex. Molecular Neurobiology, 2018, 55, p. 7216-7228. Disponible en: <https://link.springer.com/article/10.1007/s12035-018-0921-3>. Fecha de acceso: 18 jun. 2020. DOI: 10.1007/s12035-018-0921-3.
dc.identifier	1559-1182
dc.identifier	https://dx.doi.org/10.1007/s12035-018-0921-3
dc.identifier.uri	http://hdl.handle.net/20.500.12328/1589
dc.description	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.
dc.format	13
dc.format	application/pdf
dc.language	eng
dc.publisher	Molecular Neurobiology
dc.relation	Springer Nature
dc.relation	55;
dc.relation	info:eu-repo/grantAgreement/ES/1PE/ICTI2013-2016/SAF2015-71026-R
dc.relation	info:eu-repo/grantAgreement/ES/1PE/ICTI2013-2016/BFU2015-70454-REDT
dc.relation	info:eu-repo/grantAgreement/ES/1PE/ICTI2013-2016/SAF2013-45887-R
dc.relation	info:eu-repo/grantAgreement/ES/1PE/ICTI2013-2016/SAF2014-52223-C2-1-R
dc.relation	info:eu-repo/grantAgreement/ES/1PE/ICTI2013-2016/SAF2014-52223-C2-2-R
dc.relation	info:eu-repo/grantAgreement/EC/FP7/281854
dc.rights	This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
dc.rights	http://creativecommons.org/licenses/by/4.0/
dc.subject	Àcids grassos
dc.subject	Neurones
dc.subject	Hormones
dc.subject	Somatotropina
dc.subject	Hipotàlem
dc.subject	Ácidos grasos
dc.subject	Neuronas
dc.subject	Hormonas
dc.subject	Somatotropina
dc.subject	Hipotálamo
dc.subject	Fatty acids
dc.subject	Neurons
dc.subject	Hormones
dc.subject	Somatotropin
dc.subject	Hypothalamus
dc.subject	61
dc.title	Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/acceptedVersion

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