2024-03-28T13:48:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1769312022-06-01T12:30:14Zcom_10261_105com_10261_1col_10261_358
Mir, Joan Francesc
Zagmutt, Sebastián
Lichtenstein, Mathieu
García-Villoria, Judit
Weber, Minéia
Gracia, Ana
Fabriàs, Gemma
Casas, Josefina
López, Miguel
Casals, Núria
Ribes, Antònia
Suñol, Cristina
Herrero, Laura
Serra, Dolors
2019-02-28T11:57:57Z
2019-02-28T11:57:57Z
2018-09
Molecular Neurobiology 55(9): 7216–7228 (2018)
0893-7648
http://hdl.handle.net/10261/176931
10.1007/s12035-018-0921-3
1559-1182
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/100008666
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100010801
29396649
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.
eng
http:// creativecommons.org/licenses/by/4.0/
openAccess
Ghrelin
GABA
Fatty acid oxidation
CPT1a
Cortical neurons
Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex
artículo