CD36 Induces Inflammation by Promoting Ferroptosis in Pancreas, Epididymal Adipose Tissue, and Adipose Tissue Macrophages in Obesity-Related Severe Acute Pancreatitis

作者：R Zhang, Ling Xin, Xianwen Guo, Zhen Ding · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26083482 · 被引用次数：7 · 研究领域：Pancreatitis Pathology and Treatment、Pancreatic and Hepatic Oncology Research、Inflammatory Biomarkers in Disease Prognosis

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 ...