HIF-1α-PPARγ-mTORC1 signaling pathway-mediated autophagy induces inflammatory response in pancreatic cells in rats with hyperlipidemic acute pancreatitis

Objective The incidence of hyperlipidemic acute pancreatitis (HLAP) has rapidly increased in recent years in China. Autophagy has been implicated in the inflammatory response of pancreatic cells in HLAP, but the molecular mechanisms remain unclear. Methods In this study, the role of HIF-1 alpha-PPAR gamma-mTORC1 pathway-mediated autophagy in the inflammatory response of pancreatic cells and the underlying molecular mechanism were investigated in a rat model of HLAP using immunohistochemistry, ELISA, electron microscopy, and western blot analysis. Results The results revealed that autophagy was significantly increased and pancreatic injury was exacerbated in HLAP rats, and the inflammatory response was further exacerbated by treatment with rapamycin but relieved by treatment with 3-MA. Hyperlipidemia induced upregulation of HIF-1 alpha and downregulation of PPAR gamma, which in turn led to an increase in autophagy and consequently exacerbation of the inflammatory response of pancreatic cells. Conclusions HIF-1 alpha-PPAR gamma-mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in HLAP, and interference with the HIF-1 alpha-PPAR gamma-mTOR pathway can serve as a new strategy for the prevention and treatment of HLAP.