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oai:docta.ucm.es:20.500.14352/949142024-09-03T00:07:55Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Martins, Luis author Fernández Mallo, Diana author Garrido Novelle, Marta author Vázquez, María author Tena Sempere, Manuel author Nogueiras, Rubén author López, Miguel author Diéguez, Carlos author 2012 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. 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 1932-6203 10.1371/journal.pone.0046923 https://hdl.handle.net/20.500.14352/94914 https://doi.org/10.1371/journal.pone.0046923 Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin