白脂素通过NRF2参与肥胖和运动减肥过程中小鼠肝脂合成的调控  

Involvement of asprosin in regulation of liver lipid synthesis in mice under obesity and exercise weight loss through NRF2

作　　者：赵泽宇 刘淼 韩祎 姚婷婷[1] 李涛[3] 李壬冬 衣雪洁 马铁[1] ZHANG Zeyu;LIU Miao;HAN Yi;YAO Tingting;LI Tao;LI Rendong;YI Xue-hie;MA Tie(College of Exercise and Health,Shenyang Sport University,Shenyang 110102,China;Shanghai Elite Sport Training Administrative Center,Shanghai 202162,China;Laboratory Management Center,Shenyang Sport University,Shenyang 110102,China;Physical Education Department,Shenyang University of Chemical Technology,Shenyang 110142,Chi-na;Centre of Sports Social Science Research,Shenyang Sport University,Shenyang 110102,China)

机构地区：[1]沈阳体育学院运动健康学院,辽宁沈阳110102 [2]上海市竞技体育训练管理中心训练处,上海202162 [3]沈阳体育学院实验室管理中心,辽宁沈阳110102 [4]沈阳化工大学,辽宁沈阳110142 [5]沈阳体育学院体育社会科学研究中心,辽宁沈阳110102

出　　处：《中国病理生理杂志》2025年第4期732-742,共11页Chinese Journal of Pathophysiology

基　　金：辽宁省教育厅2021年度科学研究经费项目(面上项目)(No.LJKZ1051)。

摘　　要：目的:探索白脂素(asprosin,ASP)对肝脏脂质合成的调控作用及途径,探究肥胖和运动减肥状态下肝脏脂质合成代谢改变与ASP及其下游途径关系。方法:将雄性C57BL/6J小鼠随机分为野生(wild-type,WT)组、WT+ASP组、敲除(knockout,KO)组和KO+ASP组。KO组和KO+ASP组为ASP基因杂合KO小鼠,在取材前1个月对WT+ASP和KO+ASP组小鼠腹腔注射ASP重组蛋白。另取雄性C57BL/6J小鼠,随机分为正常对照(normal control,NC)组、高脂饮食(high-fat diet,HFD)组和HFD+运动组。HFD和HFD+运动组小鼠持续HFD喂养肥胖后,HFD+运动组小鼠进行中等强度有氧运动8周。取小鼠肝脏,采用Western blot和RT-qPCR检测小鼠肝脏中ASP通路及肝脏脂质合成相关分子的mRNA和蛋白水平;采用ELISA检测肝脏甘油三酯(triglycerol,TG)和环磷酸腺苷(cAMP)水平;HE染色和油红O染色观察肝组织病理变化。结果:(1)相较于WT组,KO组小鼠肝指数和肝脏TG水平显著升高,肝脏cAMP水平及ASP、成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)和核因子E2相关因子2(nuclear factor E2-related factor 2,NRF2)的mRNA和蛋白水平均显著降低,硬脂酰辅酶A去饱和酶1(stearoylcoenzyme A desaturase 1,SCD1)和脂肪酸合成酶(fatty acid synthase,FASN)的mRNA和蛋白水平显著升高;WT+ASP组小鼠肝指数和肝脏TG水平显著降低,肝脏SCD1和FASN的mRNA和蛋白水平显著降低,cAMP水平及NRF2的蛋白和mRNA水平显著升高,FGF21的mRNA水平显著下降。(2)相较于KO组,KO+ASP组小鼠肝脏TG水平显著降低,cAMP水平及ASP、FGF21和NRF2的mRNA和蛋白水平显著升高,SCD1和FASN的mRNA和蛋白水平显著降低。(3)与NC组相比,HFD组小鼠肝脏TG水平升高,cAMP及NRF2的mRNA和蛋白水平均显著降低,SCD1和FASN的mRNA和蛋白水平显著升高,FGF21蛋白水平显著下降,ASP的mRNA水平显著下降,蛋白水平显著上升。(4)与HFD组相比,HFD+运动组小鼠肝脏TG水平显著降低,SCD1和FASN的mRNA和蛋白水平显著降低,cAAIM:This study aims to explore the role of asprosin(ASP)in regulating hepatic lipid anabolic metabolism,as well as the effects of ASP and its downstream pathways on hepatic lipid anabolic metabolism under obesity and exercise intervention.METHODS:To explore the effect of ASP on liver lipid synthesis under physiological condition,5-week-old male C57BL/6J were randomly divided into 4 groups:wild-type(WT)group,WT+ASP group,knockout(KO)group,and KO+ASP group.The mice in KO and KO+ASP groups were ASP gene heterozygous KO mice,and the recombinant ASP protein was intraperitoneally injected into the mice in WT+ASP and KO+ASP groups for one month before sampling.To explore the role of ASP on liver lipid synthesis under obesity and exercise intervention,5-week-old male C57BL/6J mice were randomly divided into 3 groups:normal control(NC)group,high-fat diet(HFD)group,and HFD+exercise group.After 10 weeks of HFD feeding,the mice in HFD group received no intervention,while those in HFD+exercise group underwent 8 weeks of treadmill exercise intervention.The mice in both groups were fed with HFD during the intervention period.After the interventions,liver tissues were collected from the mice.Western blot and RT-qPCR methods were used to detect the expression levels of ASP,fibroblast growth factor 21(FGF21),nuclear factor E2-related factor 2(NRF2),stearoyl-coenzyme A desaturase 1(SCD1)and fatty acid synthase(FASN)in the mouse liver.ELISA was used to detect the triglycerol(TG)and cyclic adenosine monophosphate(cAMP)levels in the mouse liver,and HE staining and oil red O staining were performed to observe the morphological changes of mouse liver tissues.RESULTS:(1)Compared with WT mice,KO mice exhibited significantly reduced body weight and liver weight,while liver index and hepatic TG levels were significantly increased.The mRNA and protein levels of cAMP,ASP,FGF21 and NRF2 in the liver were significantly decreased,whereas the mRNA and protein levels of SCD1 and FASN were significantly increased.In the WT+ASP group,liver index and

关 键 词：白脂素 核因子E2相关因子2 肝脏脂质合成 肥胖 运动 减肥 

分 类 号：R589.2[医药卫生—内分泌] R363[医药卫生—内科学] R875[医药卫生—临床医学]