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

• Published in: Molecular biology reports Vol. 50; no. 10; pp. 8497 - 8507
• Main Authors: Ma, Yumei, Li, Xiaolin, Liu, Zhilan, Xue, Xiaohong, Wang, Yaping, Ma, Yingcai
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2023; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Autophagy; Biomedical and Life Sciences; Electron microscopy; Enzyme-linked immunosorbent assay; Extracellular Matrix Biology; Histocompatibility antigen HLA; Histology; Hyperlipidemia; Hypoxia-inducible factor 1a; Immunohistochemistry; Inflammation; Life Sciences; Molecular modelling; Morphology; Original Article; Pancreas; Pancreatitis; Peroxisome proliferator-activated receptors; Rapamycin; Signal transduction; TOR protein; Hyperlipidemic acute pancreatitis; Inflammatory response; HIF-1α; Autophagy; mTORC1; PPARγ
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08639-3

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-1α–PPARγ–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-1α and downregulation of PPARγ, which in turn led to an increase in autophagy and consequently exacerbation of the inflammatory response of pancreatic cells. Conclusions HIF-1α–PPARγ–mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in HLAP, and interference with the HIF-1α–PPARγ–mTOR pathway can serve as a new strategy for the prevention and treatment of HLAP.