摘要
Severe acute pancreatitis (SAP) is mainly triggered by the abnormal activation of pancreatic enzymes. Obesity acts as an independent risk factor for SAP; however, the underlying mechanism has not been fully elucidated. In this study, SAP models were established in mice with normal and high-fat diets. Subsequently, this study examined ferroptosis and inflammatory markers in pancreas and epididymal adipose tissues. To mimic obesity-related SAP in adipose tissue macrophages (ATMs), lipopolysaccharide (LPS) and palmitic acid (PA) were introduced, and alterations in ferroptosis and inflammation were assessed. To elucidate the regulatory role of cluster of differentiation 36 (CD36) in ferroptosis, liproxstatin-1 (Lip-1) and sulfosuccinimidyl oleate sodium (SSO) were utilized for in-depth analysis in the pancreas, epididymal adipose tissues, and ATMs. Our findings suggest that obesity aggravates ferroptosis in pancreas tissue, epididymal adipose tissues, and ATMs during SAP, as evidenced by increased lipid peroxidation, elevated Fe2+ levels, and alterations in ferroptosis markers, while these alterations were regained by Lip-1. Notably, CD36 levels were significantly increased in pancreatic tissue, epididymal adipose tissue, and ATMs, indicating that CD36 promotes ferroptosis and induces inflammation. SSO treatment alleviated changes in ferroptosis markers and reduced inflammation. Western blot results showed that CD36 promoted ferroptosis through the acyl-CoA synthetase long-chain family member 4 (ACSL4)/glutathione peroxidase 4 (GPX4) axis in pancreatic tissue, while a similar regulatory role was mediated by the ferritin heavy chain 1 (FTH1)/GPX4 axis and ATMs. These findings demonstrate that CD36 induces inflammation by facilitating ferroptosis in pancreas tissue, epididymal adipose tissue, and ATMs in obesity-related SAP. The inhibition of CD36 could provide novel viewpoints for the prevention and treatment of obesity-related SAP.
摘要译文
严重的急性胰腺炎（SAP）主要是由胰腺酶异常激活引起的。肥胖是SAP的独立危险因素；但是，尚未完全阐明基本机制。在这项研究中，在正常和高脂饮食的小鼠中建立了SAP模型。随后，这项研究检查了胰腺和附睾脂肪组织中的铁凋亡和炎症标记。为了模仿脂肪组织巨噬细胞（ATM）中与肥胖相关的SAP，引入了脂多糖（LPS）和棕榈酸（PA），并评估了铁植物和炎症的改变。为了阐明分化36（CD36）簇在铁凋亡中的调节作用，用于在胰腺，表育中心腺癌组织和ATM的胰腺中进行深入分析。我们的发现表明，肥胖会加剧胰腺组织，附生脂肪组织和SAP期间的ATM的氟化作用，如脂质过氧化增加，Fe2+水平升高以及氟得到病标记的变化所证明的那样，而LIP-1则恢复了这些改变。值得注意的是，胰腺组织，附睾脂肪组织和ATM中的CD36水平显着增加，表明CD36促进了铁铁作用并诱导炎症。SSO治疗减轻了逆转录病标志物的变化和炎症减少。蛋白质印迹结果表明，CD36通过酰基-COA合成链长链家族成员4（ACSL4）/谷胱甘肽过氧化物酶4（GPX4）轴促进了铁毒性，而胰腺组织中的轴轴（GPX4）轴则是由铁蛋白重链1（FTH1）/GPX4轴和Atms介导的类似调节作用。这些发现表明，CD36通过促进胰腺组织，附睾脂肪组织和与肥胖相关SAP的ATM的氟胞菌病诱导炎症。CD36的抑制作用可以为预防和治疗与肥胖相关的SAP提供新的观点。
Ruoyi Zhang (https://orcid.org/0000-0002-1802-6896) [1];Xin Ling [2];Xianwen Guo [3];Zhen Ding [4];. CD36 Induces Inflammation by Promoting Ferroptosis in Pancreas, Epididymal Adipose Tissue, and Adipose Tissue Macrophages in Obesity-Related Severe Acute Pancreatitis[J]. International Journal of Molecular Sciences, 2025,26(8): 3482