RT Journal Article
T1 Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender
A1 Lage Fernández, Ricardo
A1 Vázquez Villar, María Jesús
A1 Varela Fernández, Luis
A1 Saha, Asish K.
A1 Vidal Puig, Antonio
A1 Nogueiras Pozo, Rubén
A1 Diéguez González, Carlos
A1 López Pérez, Miguel A.
K1 AMPK
K1 CREB
K1 Dimorphism
K1 FoxO1
AB The orexigenic effect of ghrelin is mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the hypothalamic arcuate nucleus (ARC). Recent evidence also indicates that ghrelin promotes feeding through a mechanism involving activation of hypothalamic AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase and fatty acid synthase (FAS). This results in decreased hypothalamic levels of malonyl-CoA, increased carnitine palmitoyltransferase 1 (CPT1) activity, and mitochondrial production of reactive oxygen species. We evaluated whether these molecular events are part of a unique signaling cascade or whether they represent alternative pathways mediating the orexigenic effect of ghrelin. Moreover, we examined the gender dependency of these mechanisms, because recent evidence has proposed that ghrelin orexigenic effect is reduced in female rats. We studied in both genders the effect of ghrelin on the expression of AgRP and NPY, as well as their transcription factors: cAMP response-element binding protein (CREB and its phosphorylated form, pCREB), forkhead box O1 (FoxO1 and its phosphorylated form, pFoxO1), and brain-specific homeobox transcription factor (BSX). In addition, to establish a mechanistic link between ghrelin, fatty acid metabolism, and neuropeptides, we evaluated the effect of ghrelin after blockage of hypothalamic fatty acid β oxidation, by using the CPT1 inhibitor etomoxir. Ghrelin-induced changes in the AMPK-CPT1 pathway are associated with increased levels of AgRP and NPY mRNA expression through modulation of BSX, pCREB, and FoxO1, as well as decreased expression of endoplasmic reticulum (ER) stress markers in a gender-independent manner. In addition, blockage of hypothalamic fatty acid β oxidation prevents the ghrelin-promoting action on AgRP and NPY mRNA expression, also in a gender-independent manner. Notably, this effect is associated with decreased BSX expression and reduced food intake. Overall, our data suggest that BSX integrates changes in neuronal metabolic status with ARC-derived neuropeptides in a gender-independent manner
PB Wiley
SN 0892-6638
YR 2010
FD 2010
LK http://hdl.handle.net/10347/32558
UL http://hdl.handle.net/10347/32558
LA eng
NO Lage, R., Vázquez, M.J., Varela, L., Saha, A.K., Vidal-Puig, A., Nogueiras, R., Diéguez, C. and López, M. (2010), Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender. The FASEB Journal, 24: 2670-2679. https://doi.org/10.1096/fj.09-150672
NO "This is the peer reviewed version of the following article: Lage, R., Vázquez, M.J., Varela, L., Saha, A.K., Vidal-Puig, A., Nogueiras, R., Diéguez, C. and López, M. (2010), Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender. The FASEB Journal, 24: 2670-2679, which has been published in final form at https://doi.org/10.1096/fj.09-150672. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited."
DS Minerva
RD 24 abr 2026