LPCAT3 protects against acinar cell ferroptosis in acute pancreatitis

AbstractAcute pancreatitis (AP) is a severe digestive disorder characterized by the abnormal activation of pancreatic enzymes, leading to pancreatic autodigestion. The incidence of AP is rising globally, with severe cases associated with high mortality rates. The pathogenesis of AP has been implicated in ferroptosis. Our study aimed to understand the role of lysophosphatidylcholine acyltransferase 3 (LPCAT3) in regulating ferroptosis in AP. We constructed a rat model and an AP cell model. LPCAT3 expression and function were assessed using immunohistochemistry, hematoxylin and eosin staining, and Western blot analysis. The effects of LPCAT3 overexpression and knockdown were investigated using viral vectors.LPCAT3 expression was significantly downregulated in AP models. Overexpression of LPCAT3 in vitro reduced markers of ferroptosis and inflammation, indicating a protective role against AP. Conversely, LPCAT3 knockdown exacerbated ferroptosis and inflammation, indicating the promising impact of LPCAT3 in inhibiting these processes.LPCAT3 was found to play a critical role in regulating ferroptosis in AP, presenting a promising therapeutic target. Overall, this work provides new insights into the molecular mechanisms underlying AP and highlights the potential of LPCAT3 in developing strategies to alleviate disease severity.