Sulforaphane ameliorates non-alcoholic fatty liver disease in mice by promoting FGF21/FGFR1 signaling pathway  

作　　者：Yi-kuan Wu Zheng-nan Ren Sheng-long Zhu Yun-zhou Wu Gang Wang Hao Zhang Wei Chen Zhao He Xian-long Ye Qi-xiao Zhai 

机构地区：[1]State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,China [2]School of Food Science and Technology,Jiangnan University,Wuxi 214122,China [3]School of Medicine,Jiangnan University,Wuxi 214122,China [4]College of Life Science,Northeast Agricultural University,Harbin 150038,China [5]National Engineering Research Center for Functional Food,Jiangnan University,Wuxi 214122,China [6]Shandong Key Laboratory of Endocrinology and Lipid Metabolism,Jinan 250021,China [7]School of Medicine,Shandong University,Jinan 250012,China [8]Ganjiang Chinese Medicine Innovation Center,Nanchang 330000,China

出　　处：《Acta Pharmacologica Sinica》2022年第6期1473-1483,共11页中国药理学报（英文版）

基　　金：This research was supported by the National Natural Science Foundation of China(Grant No.31871773 to QXZ,81600664 to XLY and 31471321 to ZH).

摘　　要：Most studies regarding the beneficial effect of sulforaphane(SFN)on non-alcoholic fatty liver disease(NAFLD)have focused on nuclear factor E2-related factor 2(Nrf2).But the molecular mechanisms underlying the beneficial effect of SFN in the treatment of NAFLD remain controversial.Fibroblast growth factor(FGF)21 is a member of the FGF family expressed mainly in liver but also in adipose tissue,muscle and pancreas,which functions as an endocrine factor and has been considered as a promising therapeutic candidate for the treatment of NAFLD.In the present study we investigated whether FGF21 was involved in the therapeutic effect of SFN against NAFLD.C57BL/6J mice were fed a high-fat diet(HFD)for 12 weeks to generate NAFLD and continued on the HFD for additional 6 weeks with or without SFN treatment.We showed that administration of SFN(0.56 g/kg)significantly ameliorated hepatic steatosis and inflammation in NAFLD mice,along with the improved glucose tolerance and insulin sensitivity,through suppressing the expression of proteins responsible for hepatic lipogenesis,while enhancing proteins for hepatic lipolysis and fatty acids oxidation.SFN administration significantly increased hepatic expression of FGFR1 and fibroblast growth factor 21(FGF21)in NAFLD mice,along with decreased phosphorylation of p38 MAPK(the downstream of FGF21).HepG2 cells were treated in vitro with FFAs(palmitic acid and oleic acid)followed by different concentrations of SFN.We showed that the effects of SFN on FGF21 and FGFR1 protein expression were replicated in FFAs-treated HepG2 cells.Moreover,the increased FGFR1 protein occurred earlier than increased FGF21 protein.Interestingly,the rapid effect of SFN on FGFR1 protein was not regulated by the FGFR1 gene transcription.Knockdown of FGFR1 and p38 genes weakened SFN-reduced lipid deposition in FFAs-treated HepG2 cells.SFN administration in combination with rmFGF21(1.5 mg/kg,i.p.,every other day)for 3 weeks further suppressed hepatic steatosis in NAFLD mice.In conclusion,SFN ameliorates lipid meta

关 键 词：non-alcoholic fatty liver disease SULFORAPHANE fibroblast growth factor 21 fibroblast growth factor receptor-1 P38MAPK insulin sensitivity 

分 类 号：R285.5[医药卫生—中药学]