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

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

机构地区：[1]Joint Research Center on Medicine,The Affiliated Xiangshan Hospital of Wenzhou Medical University,Ningbo,315700,China [2]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China [3]College of Pharmacy and Research Institute of Drug Development,Chonnam National University,Gwangju,Republic of Korea [4]School of Pharmacy,Hangzhou Normal University,Hangzhou,311121,China

出　　处：《Acta Pharmacologica Sinica》2024年第5期988-1001,共14页中国药理学报（英文版）

基　　金：support was provided by the Medical and Health Science Research Project of Zhejiang Province(2023XY164 to LJH,2022KY348 to WZ);Key Research Project of Wenzhou City(ZY2021021 to YW).

摘　　要：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.

关 键 词：non-alcoholic fatty liver disease fibroblast growth factor receptor 1 MACROPHAGES MAPKS NF-κB hepatic stellate 

分 类 号：R575.5[医药卫生—消化系统]