db/db小鼠肝细胞脂滴代谢特征的研究  

Characterization of lipid droplet metabolism in hepatocytes in db/db mice

作　　者：孙雯 徐晔 肖泓健 冯婉瑜 袁馨梦 项梦奇 陆矫 汤强[1] 张媛[1] SUN Wen;XU Ye;XIAO Hongjian(School of Sports and Health,Nanjing Sport Institute,Nanjing 210014,China)

机构地区：[1]南京体育学院运动健康学院,210014 [2]南京体育学院体育科学研究院

出　　处：《中国糖尿病杂志》2024年第12期932-940,共9页Chinese Journal of Diabetes

基　　金：国家自然科学基金(32000839);江苏省高等学校基础科学(自然科学)研究重大项目(24KJA310002);江苏省“青蓝工程”资助项目[(2021)11];江苏省研究生科研与实践创新计划(KYCX23-2380、KYCX23-2363);江苏省大学生创新创业训练计划(202310330011Z)。

摘　　要：目的比较正常BKS-db/m小鼠与T2DM模型BKS-db/db小鼠肝脏脂滴(LDs)代谢特征,研究db/db小鼠肝脏LDs代谢特征及代谢稳态失衡的分子机制。方法选取SPF级8周龄BKS-db/m(db/m组)及BKS-db/db(db/db组)小鼠各8只。检测血脂代谢,油红、HE染色评价肝脏脂质沉积程度,免疫荧光染色、Western blot法检测肝脏LDs合成分解代谢水平。结果db/db组体重、肝重、肝指数、FPG、OGTT及胰岛素耐量的血糖曲线下面积、TG、TC、HDL-C、LDL-C、FFA、甾醇调节元件结合蛋白1(SREBP1)阳性荧光面积、核转位高于db/m组(P<0.05)。db/db组原代肝细胞脂噬水平高于db/m组(P<0.05)。与db/m组比较,db/db组SREBP1、硬脂酰辅酶A去饱和酶1、围脂滴蛋白、微管相关蛋白1A/1B-轻链3、溶酶体相关膜蛋白2A、甘油三酯脂肪酶蛋白表达升高(P<0.05),p-乙酰辅酶A羧化酶(ACC)/ACC蛋白表达降低(P<0.05)。结论与正常小鼠比较,T2DM小鼠血脂异常,肝细胞脂质沉积明显,虽然LDs脂解与脂噬作用增强,分解作用显著,但LDs代谢处于合成与分解失衡状态,导致肝细胞脂质聚集。Objective To compare the hepatic lipid droplet metabolism in normal BKS-db/m mice and BKS-db/db mice,a model of type 2 diabetes mellitus(T2DM),and to investigate the characteristics of hepatic lipid droplet metabolism and the molecular mechanisms underlying the imbalance of metabolic homeostasis at the level of lipid droplet synthesis and lipid droplet catabolism in db/db mice.Methods Eight SPF 8 weeks BKS-db/m and 8 BKS-db/db mice were used in this study.The lipid metabolism level was tested.Oil red and HE staining was used to evaluate the degree of liver lipid deposition,and immunofluorescence staining and Western blot was used to observe the level of hepatic lipid droplet catabolism and metabolism.Results The body weight,liver weight,liver index,FPG,AUC of the OGTT,AUC of the ITT,TG,TC,HDL-C,LDL-C,FFA and SREBP1 positive fluorescence area and nuclear translocation were higher in db/db group than in db/m group(P<0.05).The lipophagia level of primary hepatocytes was higher in db/db group than in db/m group(P<0.05).Compared with the db/m group,the expressions of SREBP1,SCD1,PLIN2,LC3,LAMP2A and ATGL protein increased(P<0.05),while the expression of p-ACC/ACC protein decreased in the db/db group(P<0.05).Conclusions Compared with normal mice,T2DM mice had dyslipidemiaand marked hepatocellular lipid deposition.Although lipid droplet lipolysis and lipophagy were enhanced and catabolism was significant,the lipid droplet metabolism was in a state of imbalance between synthesis and catabolism,and the synthesis of lipid droplets was greater than that of catabolism,which led to the aggregation of hepatocellular lipids.

关 键 词：糖尿病 2型 肝脏脂质沉积 脂滴代谢 脂解 脂噬 

分 类 号：R587.1[医药卫生—内分泌]