Hypothalamic mTOR Signaling Mediates the Orexigenic Action of Ghrelin
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Autor
Martins, Luis
Fernández-Mayo, Diana
Novelle, Marta G.
Vázquez, María J.
Nogeiras, Rubén
López, Miguel
Diéguez, Carlos
Tena-Sempere, Manuel
Editor
Public Library Of Science (PLOS)Fecha
2012Materia
GhrelinmTOR
Hypothalamus
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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