ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1577669
CPT1A Mediated Preservation of Mitochondrial Inhibits Pyroptosis in Pancreatic Acinar Cells
Provisionally accepted
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China, Chengdu, China
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Carnitine palmitoyltransferase 1A (CPT1A) is crucial for mitochondrial function, and its dysfunction has been linked to the development of several diseases. However, the role of CPT1A in severe acute pancreatitis (SAP) and its underlying mechanisms remain unclear. Mitochondrial damage-mediated pyroptosis has been identified as a critical factor in pancreatic acinar cell death during SAP. This study aimed to evaluate the protective role of CPT1A in SAP and to investigate its association with pancreatic acinar cell pyroptosis, along with the underlying mechanisms involved during disease progression. Experimental SAP models were established in male C57BL/6 mice via retrograde injection of 3% sodium taurocholate (STC) into the pancreatic duct or by treating primary acinar cells with 5 mM STC. Changes in Cpt1a mRNA and protein expression were assessed in the SAP models. Pancreatic pyroptosis was characterized by the activation of NLRP3 inflammasome-related proteins. Further, Cpt1a was knocked down using siRNA or inhibited by etomoxir in 266-6 cells. Cell viability was assessed by Hoechst/PI staining, western blotting, and LDH release assays. The impact of CPT1A activators (C75 and L-carnitine) on mitochondrial function (ΔΨm, mtROS, and ox-mtDNA release) was evaluated in pancreatic acinar cells. Elevated CPT1A expression preserved mitochondrial function in STC-exposed acinar cells and reduced STC-induced pyroptosis in a GSDMD-dependent manner. These findings reveal a novel protective mechanism of CPT1A in SAP, involving mitochondrial functional protection and suppression of NLRP3/GSDMD-mediated pancreatic pyroptosis.
Keywords: acute pancreatitis, CPT1a, Mitochondrial dysfunction, pyroptosis, L-Carnitine
Received: 16 Feb 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Liu, Liu, Yu, Tian, Li, Gao, Zhang and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wen Huang, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China, Chengdu, China
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