肥胖是胰腺癌(PC)的一个重要风险因素。巨噬细胞诱导的炎症在肥胖相关的癌变和疾病进展中起到关键作用，然而，其潜在的分子机制尚不清楚。在本研究中，我们发现脂肪酸结合蛋白4(FABP4)在肥胖患者血清中过度表达，并且与整体生存率差相关。体内外实验证明，FABP4诱导巨噬细胞相关炎症，在肥胖条件下促进癌细胞的迁移、侵袭和转移。机制上，FABP4参与将饱和脂肪酸转运至巨噬细胞中，以一种依赖于caspase-1/GSDMD的方式诱导巨噬细胞的红色火焰死亡，同时在巨噬细胞中介导NOD样受体热蛋白领域相关蛋白3(NLRP3)/IL-1β轴，进一步调节上皮间质转变信号，促进PC细胞的迁移、侵袭和转移。我们的结果表明，在肥胖条件下，FABP4在巨噬细胞中是调节NLRP3/IL-1β轴、促进PC进展的关键调节因子，可以作为治疗肥胖胰腺癌患者的一个有前景的分子靶点。版权所有 © 2023 Elsevier B.V.发表

Obesity is an essential risk factor for pancreatic cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote cancer cell migration, invasion and metastasis under obese condition. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages pyroptosis in a caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1β axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1β axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity.Copyright © 2023. Published by Elsevier B.V.