TY - Jour A2 - Sipert，Carla Au - Hu，Xiang Au - 周，景奥 - 宋，沙沙AU - 孔，文坳，延川坳 - 陈，陆禄·奥 - 曾，天 -SHU PY - 2020 DA - 2020/09/16 TI - TLR4 / AP-1针对性的抗炎干预衰减胰岛素敏感性和肝脏脂肪变性SP - 2960517 VL - 2020 AB - 胰岛素抗性已被证明是许多人的常见发病机制代谢疾病。梅纳氏炎症是胰岛素抵抗的重要特征之一。巨噬细胞极化介导梅花料的生产和开发。Toll样受体4（TLR4）介导巨噬细胞活动，可能是免疫和新陈代谢的交叉点，但是细节机制可能无法完全理解。活化蛋白1（AP1）信号通路在巨噬细胞活化介导的炎症中非常重要。然而，目前尚不清楚AP1信号通路是否在肝脏中介导代谢炎症。我们旨在探讨巨噬细胞TLR4-AP1信号通路对肝细胞代谢炎症，胰岛素敏感性和脂质沉积的影响，以及探讨TLR4-AP1的潜力作为胰岛素抵抗和肝脏脂肪变性的新干预靶点。通过慢病毒siRNA转染在Raw264.7细胞中沉默TLR4和AP1。 In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes. SN - 0962-9351 UR - https://doi.org/10.1155/2020/2960517 DO - 10.1155/2020/2960517 JF - Mediators of Inflammation PB - Hindawi KW - ER -