Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.

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...

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Autores principales:	Luís Martins, Diana Fernández-Mallo, Marta G Novelle, María J Vázquez, Manuel Tena-Sempere, Rubén Nogueiras, Miguel López, Carlos Diéguez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee0d34b46e7b4b5c856607bd07fa97d9
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spelling	oai:doaj.org-article:ee0d34b46e7b4b5c856607bd07fa97d92021-11-18T08:12:42ZHypothalamic mTOR signaling mediates the orexigenic action of ghrelin.1932-620310.1371/journal.pone.0046923https://doaj.org/article/ee0d34b46e7b4b5c856607bd07fa97d92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056530/?tool=EBIhttps://doaj.org/toc/1932-6203Current 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.Luís MartinsDiana Fernández-MalloMarta G NovelleMaría J VázquezManuel Tena-SempereRubén NogueirasMiguel LópezCarlos DiéguezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46923 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luís Martins Diana Fernández-Mallo Marta G Novelle María J Vázquez Manuel Tena-Sempere Rubén Nogueiras Miguel López Carlos Diéguez Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
description	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.
format	article
author	Luís Martins Diana Fernández-Mallo Marta G Novelle María J Vázquez Manuel Tena-Sempere Rubén Nogueiras Miguel López Carlos Diéguez
author_facet	Luís Martins Diana Fernández-Mallo Marta G Novelle María J Vázquez Manuel Tena-Sempere Rubén Nogueiras Miguel López Carlos Diéguez
author_sort	Luís Martins
title	Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
title_short	Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
title_full	Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
title_fullStr	Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
title_full_unstemmed	Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.
title_sort	hypothalamic mtor signaling mediates the orexigenic action of ghrelin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/ee0d34b46e7b4b5c856607bd07fa97d9
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Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.

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