β3AR通路活化诱导FGF21表达促进白色脂肪组织棕色化  

Browning of white adipose tissues is promoted by FGF21 induced by the activatedβ3AR pathway

作　　者：王文递 马蓓蓓 吴惠文[1] WANG Wendi;MA Beibei;WU Huiwen(不详;Fenyang College of Shanxi Medical University,Shanxi,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院,山西省汾阳市032200

出　　处：《河北医药》2023年第7期1035-1038,共4页Hebei Medical Journal

基　　金：山西省重点研发计划项目(编号:201903D321219);山西医科大学汾阳学院院级科研项目(编号:2019D06)。

摘　　要：目的通过活化β3AR-PKA通路,探讨成纤维细胞生长因子21(FGF21)对白色脂肪组织(WAT)棕色化的影响。方法C57BL/6小鼠分别采用标准小鼠饲料(16只)及45%千卡脂肪高脂饲料(16只)喂养。12周后,标准饲料喂养小鼠随机分为2组:对照组(NC组)注射0.9%氯化钠溶液,注射CL316,243组(CL组)注射CL316,243(1 mg/kg);高脂饲料喂养小鼠随机分为2组:高脂饮食组(HFD组)注射0.9%氯化钠溶液,高脂饮食注射CL316,243组(HFD+CL组)注射CL316,243(1 mg/kg)。14周后,Western blot检测WAT蛋白激酶A(PKA)及棕色化相关蛋白(FGF21、PGC-1α及UCP1)表达;观察肝脏及脂肪组织病理学变化。培养3T3-L1前脂肪细胞,诱导成熟后分为3组:NC组,DMEM培养液;CL组,培养液+10μmol/L CL316,243;SU+CL组,培养液+50μmol/L SU5402+10μmol/L CL316,243。48 h后,检测蛋白激酶A(PKA)及棕色化相关蛋白表达,免疫荧光检测线粒体表达。结果与NC组比较,CL组PKA水平及棕色化相关蛋白升高;与CL组比较,HFD+CL组PKA水平及棕色化相关蛋白降低;而HFD+CL组相关蛋白表达高于HFD组。体外实验,与NC组比较,CL组及CL+SU组PKA水平显著升高;CL+SU组较CL组棕色化相关蛋白表达降低;免疫荧光结果显示,与NC组比较,CL组线粒体表达增多;而SU+CL组线粒体表达较CL组减少。结论活化β3AR-PKA通路可增加WAT中FGF21分泌,进而上调PGC-1α及UCP1表达,促进WAT棕色化。Objective To investigate the effect of fibroblast growth factor 21(FGF21)on the browning of white adipose tissue(WAT)by activating theβ3AR-PKA pathway.Methods C57BL/6 mice were fed with standard diet(n=16)and 45%kcal high-fat diet(n=16).After 12 weeks of feeding,mice fed a standard diet were randomly divided into control group(NC group)and CL316,243 group(CL group).They were injected with 0.9%NaCl solution and CL316,2431mg/kg,respectively.Mice fed a high-fat diet were randomly divided into high-fat diet group(HFD group)and HFD+CL group.They were injected with 0.9%NaCl solution and CL316,2431mg/kg,respectively.After 14 weeks,the expression levels of WAT protein kinase A(PKA)and browning-related proteins(FGF21,PGC-1αand UCP1)were detected by Western blot.Pathological changes of the liver and adipose tissues were observed.The 3T3-L1 preadipocyte cell line was cultured and induced into maturation.Subsequently,cells were divided into three groups,which were induced in DMEM(NC group),DMEM+10μmol/L CL316,243(CL group)and DMEM+50μmol/L SU5402+10μmol/L CL316,243(SU+CL group).After cell culture for 48h,expression levels of PKA and browning-related proteins were detected,and mitochondrial expression was detected by immunofluorescence.Results Compared with those of the NC group,PKA and browning-related proteins in the CL group were significantly up-regulated,but which in HFD+CL group were significantly down-regulated compared with CL group.Their expression levels were significantly up-regulated in HFD+CL group than those of HFD group.In vitro experiments showed that PKA was significantly up-regulated in CL and CL+SU group than that in NC group,and browning-related proteins were significantly down-regulated in CL+SU group than in CL group.Immunofluorescence data revealed that the positive expression of mitochondria in CL group was significantly higher than that in NC group,which was significantly lower in CL+SU group than in CL group.Conclusion Activation of theβ3AR-PKA pathway can increase the secretion of FGF21 in WAT

关 键 词：WAT棕色化 β3AR通路 FGF21 PGC-1Α UCP1 

分 类 号：R589.25[医药卫生—内分泌]