TY - JOUR AB - Orexin A and B are multifunctional neuropeptides that are involved in the regulation of food intake, energy metabolism, glucose regulation and wakefulness. They signal through two G-protein‑coupled receptors (GPCR): orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Previous studies have shown that orexins interact with PI3K/AKT signaling pathways through OX1R-coupling in other cell types, but are seldom involved in hepatocytes. In the present study, reverse transcription (RT)-PCR and western blot analysis revealed that OX1R mRNA expression and activation in rat hepatocytes in vitro were upregulated by exogenous orexin A (10-10 to 10-6 M) in a dose-dependent manner. The result showed that orexin A affects increasing cell proliferation and protects cells from apoptosis. Additionally, inhibition studies showed that orexin A induced forkhead box O1 (FoxO1) and mammalian target of rapamycin 1 (mTORC1) phosphorylation, while OX1R antagonist (SB334867, 10-6 M), AKT antagonist (PF-04691502, 10-6 M), Foxo1 inhibitor (AS1842856, 10-6 M) or mTORC1 inhibitor (everolimus, 10-5 M) blocked these effects of orexin A. The results of the present study showed a possible effect of orexin A on cell apoptosis in regulating Foxo1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in rat hepatocytes. AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China AU - Ju,Shu-Jing AU - Zhao,Yuyan AU - Chang,Xiaocen AU - Guo,Lei DA - 2014/07/01 DO - 10.3892/ijmm.2014.1769 EP - 159 IS - 1 JO - Int J Mol Med KW - orexin A orexin receptor 1 PI3K/AKT forkhead box O1 mammalian target of rapamycin 1 cell apoptosis PY - 2014 SN - 1107-3756 1791-244X SP - 153 ST - Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes T2 - International Journal of Molecular Medicine TI - Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes UR - https://doi.org/10.3892/ijmm.2014.1769 VL - 34 ER -