FOXO1 directly stimulates transcription of the NPY gene, encoding neuropeptide-Y, in hypothalamic orexigenic neurons. NPY stimulates food intake and weight gain. Insulin and leptin, through PI3K/AKT signaling, inhibit FOXO1-mediated upregulation of NPY expression (Kim et al. 2006). NPY may act through a positive feedback loop to increase the transcriptional activity of FOXO1 through the PKA/CREB pathway (Hong et al. 2012).