Objectives: 

Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1)/p53 and AMPactivated 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.

Materials: 

Male Sprague-Dawley rats were administered Rapamycin and/or Ghrelin by intracerebroventricular cannula. Intake was monitored and the hypothalamus or the whole brain were dissected for analysis by Western blotting or for studies of in situ hybridization respectively.

Results: 

Central administration of ghrelin activates the mTOR pathway, increasing the levels of downstream targets such as S6K1 and S6. 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).

Conclusions: 

Ghrelin elicits a marked upregulation of the hypothalamic mammalian target of rapamycin (mTOR) signaling pathway. Taken together, these data indicate that, in addition to previous reported mechanisms, ghrelin also promotes feeding through modulation of hypothalamic mTOR pathway.