Title |
Hypothalamic mTOR Signaling Mediates the Orexigenic Action of Ghrelin
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Published in |
PLOS ONE, October 2012
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DOI | 10.1371/journal.pone.0046923 |
Pubmed ID | |
Authors |
Luís Martins, Diana Fernández-Mallo, Marta G. Novelle, María J. Vázquez, Manuel Tena-Sempere, Rubén Nogueiras, Miguel López, Carlos Diéguez |
Abstract |
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. |
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Country | Count | As % |
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Unknown | 4 | 100% |
Demographic breakdown
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Members of the public | 3 | 75% |
Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
Geographical breakdown
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Spain | 2 | 2% |
Germany | 1 | 1% |
Unknown | 92 | 97% |
Demographic breakdown
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Student > Ph. D. Student | 21 | 22% |
Student > Master | 13 | 14% |
Student > Bachelor | 11 | 12% |
Professor > Associate Professor | 9 | 9% |
Student > Doctoral Student | 8 | 8% |
Other | 19 | 20% |
Unknown | 14 | 15% |
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Biochemistry, Genetics and Molecular Biology | 15 | 16% |
Medicine and Dentistry | 11 | 12% |
Neuroscience | 5 | 5% |
Philosophy | 2 | 2% |
Other | 5 | 5% |
Unknown | 19 | 20% |