摘要
本研究目的是为了探究7-酮基胆甾醇-9-羧基壬烷(OXL-1)对油酸诱导的HepG2细胞形成的非酒精性脂肪性肝病(NAFLD)细胞模型中脂质生成的潜在抑制作用。油红染色显示OXL-1能显著降低油酸诱导的甘油三酯(TG)和总胆固醇(TC)的脂质生成。基因芯片分析发现,与对照组相比,HepG2细胞经OXL-1处理后固醇调节元件结合蛋白1c(SREBP1c)、脂肪酸合酶(FAS)及乙酰辅酶a羧化酶α(ACCα)转录表达显著降低。相比较于对照组,OXL-1组甘油三脂减少56. 87%±9. 08%(P <0. 01),总胆固醇减少24. 96%±5. 45%(P <0. 01)。同时也使SREBP1c、FAS和ACCα蛋白质表达水平降低。OXL-1组相比OA组,其SREBP1c、FAS和ACCα的蛋白质表达分别下调52. 62%±6. 38%(P <0. 01)、51. 14%±8. 75%(P <0. 01)和19. 46%±3. 64%(P <0. 05)。结果说明,OXL-1可能经由SREBP1c、FAS和ACCα的转录和蛋白质水平的调控作用来阻止OA诱导的脂质蓄积。综上结果揭示,OXL-1可能在非酒精性脂肪肝病细胞模型中作为一种阻止脂质积累的新型化合物。
This study aimed to investigate the mechanisms underlying the inhibitory effects of 7-ketocholesteryl-9-carboxynonanoate（ OXL-1） on oleic acid（ OA）-induced lipogenesis in a wellreplicated HepG2 cell model of nonalcoholic fatty liver disease（ NAFLD）. Oil Red O（ ORO） staining showed that OXL-1 significantly decreased OA-induced lipogenesis of triglycerides（ TG） and total cholesterol（ TC）. Microarray analysis revealed that the mRNA levels of sterol regulatory element binding protein 1 c（ SREBP1 c）,fatty acid synthase（ FAS）,and acetyl-coA carboxylase alpha（ ACCα） were reduced in response to OXL-1 compared with the control treatment. Compared to the OA group,the levels of TG and TC in HepG2 cells were decreased by 56. 87% ± 9. 08% and 24. 96% ± 5. 45%（ P〈 0. 01） respectively in the OXL-1 group. This effect was accompanied by reduced expression of SREBP1 c,FAS,and ACCα in the OXL-1 group compared with that in the OA group. The protein levels of SREBP1 c,FAS and ACCα in OXL-1 group were consistently downregulated by 52. 62% ± 6. 38%（ P 〈0. 01）,51. 14% ± 8. 75%（ P 〈0. 01）,and 19. 46% ± 3. 64%（ P 〈0. 05）,respectively,as compared with those in the OA group. The results showed that OXL-1 might prevent lipid accumulation induced by OA via downregulating the expression of SREBP1 c,FAS and ACCα. Taken together,these results indicate that OXL-1 could be used as a new compound to prevent lipid accumulation in HepG2 cell models of NAFLD.
作者
兰佳欣
乔辉
付常振
王仁军
路遥
迟彦
赵伟
刘庆平
LAN Jia-Xin;QIAO Hui;FU Chang-Zhen;WANG Ren-Jun;LU Yao;CHI Yan;ZHAO Wei;LIU Qing-Ping(Key Laboratory of Carbohydrate and Lipid Metabolism Research,College of Life Science and Technology,Dalian University 10 Xuefu Avenue,Dalian Economic and Technological Development Zone,Liaoning 116622,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2018年第11期1239-1247,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
Supported by National Natural Science Foundation of China(No.81673494)~~
