温州医科大学Yi Wang等研究人员合作发现，巨噬细胞特异性FGFR1基因缺失可通过抑制MAPK/TNF通路缓解高脂饮食诱发的肝脏炎症。这一研究成果于2024年1月26日在线发表于国际学术期刊《中国药理学报》上。

研究人员调查了成纤维细胞生长因子受体 1（FGFR1）在非酒精性脂肪肝（NAFLD）发病机制中的作用，结果表明，高脂饮食（HFD）会增加小鼠肝脏中p-FGFR1的水平，而这与巨噬细胞浸润增加有关。此外，巨噬细胞特异性FGFR1基因敲除或服用FGFR1抑制剂，可显著保护肝脏免受高脂饮食引起的脂质积累、纤维化和炎症反应的影响。

机理研究表明，巨噬细胞特异性FGFR1基因敲除通过抑制MAPK和TNF信号通路的激活，减轻了HFD诱导的肝脏炎症，并减少了肝细胞中的脂肪沉积，从而抑制了肝星状细胞的活化。总之，这些研究结果表明，FGFR1可以通过抑制巨噬细胞中MAPK/TNF介导的炎症反应，来保护高密度脂蛋白胆固醇喂养小鼠的肝脏。因此，FGFR1可作为预防非酒精性脂肪肝发生和发展的靶点。

据悉，NAFLD是一种常见的代谢性疾病，与肥胖引起的慢性炎症密切相关。巨噬细胞活化和巨噬细胞引起的炎症在非酒精性脂肪肝的发生和发展中，起着至关重要的作用。此外，FGFR1已被证实在巨噬细胞活化过程中发挥重要作用。

附：英文原文

Title: Macrophage-specific FGFR1 deletion alleviates high-fat-diet-induced liver inflammation by inhibiting the MAPKs/TNF pathways

Author: Zhao, Yan-ni, Liu, Zhou-di, Yan, Tao, Xu, Ting-xin, Jin, Tian-yang, Jiang, Yong-sheng, Zuo, Wei, Lee, Kwang Youl, Huang, Li-jiang, Wang, Yi

Issue&Volume: 2024-01-26

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease that is substantially associated with obesity-induced chronic inflammation. Macrophage activation and macrophage-medicated inflammation play crucial roles in the development and progression of NAFLD. Furthermore, fibroblast growth factor receptor 1 (FGFR1) has been shown to be essentially involved in macrophage activation. This study investigated the role of FGFR1 in the NAFLD pathogenesis and indicated that a high-fat diet (HFD) increased p-FGFR1 levels in the mouse liver, which is associated with increased macrophage infiltration. In addition, macrophage-specific FGFR1 knockout or administration of FGFR1 inhibitor markedly protected the liver from HFD-induced lipid accumulation, fibrosis, and inflammatory responses. The mechanistic study showed that macrophage-specific FGFR1 knockout alleviated HFD-induced liver inflammation by suppressing the activation of MAPKs and TNF signaling pathways and reduced fat deposition in hepatocytes, thereby inhibiting the activation of hepatic stellate cells. In conclusion, the results of this research revealed that FGFR1 could protect the liver of HFD-fed mice by inhibiting MAPKs/TNF-mediated inflammatory responses in macrophages. Therefore, FGFR1 can be employed as a target to prevent the development and progression of NAFLD.

DOI: 10.1038/s41401-024-01226-7

Source: https://www.nature.com/articles/s41401-024-01226-7