固醇调节元件结合蛋白1c在高脂致骨骼肌细胞胰岛素抵抗炎症机制中作用的研究  

The role of sterol regulatory element binding protein-1c in inflammatory mechanisms of palmitate acid-induced skeletal muscle cell insulin resistance

作　　者：吴文君 任烨 徐湘 庄寒秋 许岚 WU Wenjun;REN Ye;XU Xiang(Department of Endocrinology,Wuxi People’s Hospital of Nanjing Medical University,Wuxi 214023,China)

机构地区：[1]南京医科大学附属无锡人民医院内分泌科,214023

出　　处：《中国糖尿病杂志》2022年第4期277-283,共7页Chinese Journal of Diabetes

基　　金：国家自然科学青年基金(81500630);江苏省高层次卫生人才“六个一工程”拔尖人才科研项目(LGY2019018);无锡市太湖人才计划高层次人才培养项目(BJ2020005)。

摘　　要：目的探讨高脂致骨骼肌细胞胰岛素抵抗中固醇调节元件结合蛋白1c(SREBP-1c)与TNF-α表达的相关性。方法L6肌管细胞不同处理后,采用2-NBDG法检测葡萄糖摄取水平,实时荧光定量PCR和Western blot法检测SREBP-1c、TNF-α的mRNA和蛋白表达。高脂喂养C57BL/6雄鼠诱导成IR模型,采用二甲双胍干预,检测腓肠肌组织TNF-α蛋白表达。结果L6肌管细胞经棕榈酸处理或过表达SREBP-1c后葡萄糖摄取降低(P<0.05),SREBP-1c、TNF-αmRNA和蛋白表达升高(P<0.05);二甲双胍干预或沉默SREBP-1c表达显示相反的变化(P<0.05)。二甲双胍作用下过表达SREBP-1c,葡萄糖摄取降低(P<0.05),TNF-αmRNA和蛋白表达升高(P<0.05)。TNF-α在高脂喂养小鼠的腓肠肌组织中表达升高(P<0.05),二甲双胍干预后表达降低(P<0.05)。结论SREBP-1c与高脂时TNF-α表达增加相关,可能参与炎症信号通路的间接调控。Objective To explore the expression relationship between sterol regulatory element binding protein-1c(SREBP-1c)and tumor necrosis factor α(TNF-α)in skeletal muscle insulin resistance(IR).Methods The glucose uptake was detected by 2-NBDG assay in L6 myotube cells after different treatment.The mRNA expression of SREBP-1c and TNF-α were detected by quantitative real-time PCR and the protein levels of them were measured by Western blot.Male C57 BL/6 mice were fed on a high-fat diet to induce IR model and then treated with metformin.The protein expression of TNF-α in gastrocnemius was detected.Results The glucose uptake was decreased(P<0.05),and the mRNA and protein levels of SREBP-1c and TNF-α were significantly increased in L6 myotube cells after PA treatment or SREBP-1c overexpression(P<0.05).Metformin treatment or SREBP-1c knockdown increased the glucose uptake,and decreased expressions of SREBP-1c and TNF-α(P<0.05).The glucose uptake was decreased(P<0.05),and the mRNA and protein levels of TNF-α were significantly increased under Metformin treatment and SREBP-1c overexpression(P<0.05).The expression of TNF-αwas increased in the gastrocnemius in high-fat mice and decreased after Metformin intervention(P<0.05).Conclusion SREBP-1c was associated with increased expression of TNF-α in skeletal muscleunder PA-induced insulin resistance.It may participate in the indirect regulation of inflammatory signaling pathways.

关 键 词：固醇调节元件结合蛋白1C 骨骼肌 胰岛素抵抗 肿瘤坏死因子Α 

分 类 号：R587.1[医药卫生—内分泌]