GHRL and major depressive disorder: For instance, evidence suggests ghrelin has an impact on the mammalian target of rapamycin (mTOR) signaling pathway; mTOR is remarkable for its role in cancer, diabetes, depression, and obesity. Early studies have shown a response in this pathway to circulating levels of ghrelin [14]. The orexigenic mechanism of ghrelin also works through alterations of sirtuin 1 (SIRT1), p53, and adenosine monophosphate-activated protein kinase (AMPK); the triggered response is an increase in the agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus [15].