RT Journal Article
T1 Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin
A1 Martins, Luis
A1 Fernández Mallo, Diana
A1 Garrido Novelle, Marta
A1 Vázquez, María
A1 Tena Sempere, Manuel
A1 Nogueiras, Rubén
A1 López, Miguel
A1 Diéguez, Carlos
AB Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1)/p53 and AMP-activated protein kinase (AMPK) pathways, which ultimately increase the expression of agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARC). However, there is a paucity of data about the possible action of ghrelin on alternative metabolic pathways at this level. Here, we demonstrate that ghrelin elicits a marked upregulation of the hypothalamic mammalian target of rapamycin (mTOR) signaling pathway. Of note, central inhibition of mTOR signaling with rapamycin decreased ghrelin’s orexigenic action and normalized the mRNA expression of AgRP and NPY, as well as their key downstream transcription factors, namely cAMP response-element binding protein (pCREB) and forkhead box O1 (FoxO1, total and phosphorylated). Taken together, these data indicate that, in addition to previous reported mechanisms, ghrelin also promotes feeding through modulation of hypothalamic mTOR pathway.
PB Public Library of Science
SN 1932-6203
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/94914
UL https://hdl.handle.net/20.500.14352/94914
LA eng
NO Martins L, Fernández-Mallo D, Novelle MG, Vázquez MJ, Tena-Sempere M, Nogueiras R, et al. (2012) Hypothalamic mTOR Signaling Mediates the Orexigenic Action of Ghrelin. PLoS ONE 7(10): e46923. https://doi.org/10.1371/journal.pone.0046923
NO Funding: The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 281854 - the ObERStress project (ML) and 245009 - the Neurofast project (RN, CD and ML), Xunta de Galicia (ML: 10PXIB208164PR; RN: 2010/14), Junta de Andalucía (MTS: P08-CVI-03788), Instituto de Salud Carlos III (ISCIII) (ML: PS09/01880), MINECO co-funded by the FEDER Program of EU (MTS: BFU2011-25021; RN: RyC-2008-02219 and SAF2009-07049; ML: RyC-2007-00211; CD: BFU2011-29102). LM is a recipient of a fellowship from Fundação para a Ciência e Tecnologia (FCT), Portugal (SFRH/BD/65379/2009). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII.
NO Xunta de Galicia
NO Instituto de Salud Carlos III
NO European Commission
NO Junta de Andalucía
NO Ministerio de Economía y Competitividad (España)
NO Portuguese Foundation for Science and Technology
DS Docta Complutense
RD 6 abr 2025