In line with these in vivo data, SH-SY5Y human neuroblastoma cells stably overexpressing IRS-2 showed increased phosphorylation of AKT at Ser473 and analysis of mRNA levels of FoxO3a revealed significantly reduced expression as observed in the CNS of mice fed a HFD indicating that chronically elevated IR/IGF-1R signaling in neurons leads to downregulation of FoxO3a in vivo and in vitro [51]. Here, FOXO3 is linked to neuroblastoma.