Key result
Hyperlipidemia induced up-regulation of HIF-1α and down-regulation of PPARγ in rats, increasing autophagy and exacerbating the inflammatory response of pancreatic cells.
Why the study?
Autophagy has been implicated in pancreatic cell inflammatory responses in hyperlipidemic acute pancreatitis, but the molecular mechanisms remain unclear.
p-value: p=<0.05
The HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in hyperlipidemic acute pancreatitis, offering potential new therapeutic targets.
Autophagy modulation may affect experimental hyperlipidemic pancreatitis outcomes; leaves open therapeutic translation and requires human validation.
Objective: The incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing rapidly 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 the HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy in the inflammatory response of pancreatic cells and the molecular mechanism are investigated in a rat model of HLAP using immunohistochemistry, ELISA, electron microscope and Western blot analysis. Results: The results reveal that autophagy is significantly increased and pancreatic injury is exacerbated in HLAP rats, and the inflammatory response is further exacerbated by treatment with rapamycin but relieved by treatment with 3-MA. Hyperlipidemia induces up regulation of HIF-1α but down regulation of PPARγ, which in turn leads to an increase in autophagy and consequently exacerbation of inflammatory response of pancreatic cells. Conclusions: It is concluded that the 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 provide new targets for prevention and treatment of HLAP.
No takes yet. Share an insight, caveat, or question.
Ma et al. (2023) studied Hyperlipidemic acute pancreatitis (n=48). Rapamycin and 3-MA vs. HLAP without autophagy modulators, AP alone, HL alone, and normal controls was evaluated on Inflammatory response and pancreatic injury (p=<0.05). Hyperlipidemia induced up-regulation of HIF-1α and down-regulation of PPARγ in rats, increasing autophagy and exacerbating the inflammatory response of pancreatic cells.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: