吉林大学学报（医学版）2026，Vol.52Issue(4)：905-913,9.DOI:10.13481/j.1671-587X.20260403
血管生成素样蛋白6对蛋氨酸和胆碱缺乏饮食诱导的小鼠肝脏脂质沉积的改善作用及其机制
Improvement effect of angiopoietin-like protein 6 on liver lipid accumulation induced by methionine-and choline-deficient diet in mice and its mechanism
摘要
Abstract
Objective:To discuss the effect of angiopoietin-like protein 6(ANGPTL6)on improving liver lipid accumulation induced by methionine-and choline-deficient(MCD)diet in the mice,and to clarify its possible mechanism.Methods:Forty-two six-week-old C57BL/6 mice were randomly divided into control group,model group and ANGPTL6 overexpression group(ANGPTL6 group),with 14 mice in each group.After one week of adaptive feeding,the mice in control group were fed normal diet,and the mice in model group and ANGPTL6 group were fed with MCD diet for 8 weeks.One week after starting the MCD diet,adeno-associated virus serotype 8(AAV8)-green fluorescent protein(GFP)empty vector and AAV8-ANGPTL6 overexpression vector were injected into the mice in model group and ANGPTL6 group via the tail vein,respectively.The steatosis model in HepG2 cells was induced by a mixture of oleic acid(OA)and palmitic acid(PA),and the cells were divided into blank control group(BSA group),model group(OD group),ANGPTL6-treated group(OAD group)and mammalian target of rapamycin(mTOR)agonist group(OAM group).HE staining and oil red O staining were used to evaluate the liver tissue morphology and lipid deposition in the mice in various groups;kits were used to detect the levels of total cholesterol(TC)and triglyceride(TG)in liver tissue of the mice in various groups and in HepG2 cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of lipid metabolism-related genes in liver tissue of the mice in various groups and in HepG2 cells in various groups;Western blotting method was used to detect the expression levels of ANGPTL6,mTOR and phosphorylated mTOR(p-mTOR)proteins in liver tissue of the mice in various groups and in the HepG2 cells in various groups.Results:Compared with control group,the livers of the mice in model and ANGPTL groups showed severe vacuolar degeneration and abnormal lipid accumulation,and the expression levels of ANGPTL6 protein in the liver tissue were decreased(P<0.05).Compared with model group,the vacuolar degeneration and lipid accumulation in liver tissue of the mice in ANGPTL6 group were alleviated,the TG level in liver tissue was decreased(P<0.05);the expression levels of lipid synthesis-related genes sterol regulatory element binding factor 1(SREBF1)and fatty acid synthase(FASN)mRNA in liver tissue were decreased(P<0.05),and the expression levels of lipid decomposition-related genes adipose triglyceride lipase(ATGL)and carnitine palmitoyltransferase 1A(CPT1A)mRNA in liver tissue were increased(P<0.05);the expression levels of mTOR and p-mTOR proteins in liver tissue were decreased(P<0.05).Compared with BSA group,the TG level,the expression levels of FASN and acetyl-CoA carboxylase alpha(ACACA)mRNA,and the expression levels of mTOR and p-mTOR proteins in the cells in OD group were all increased(P<0.05);compared with OD group,the TG level,the expression levels of FASN and ACACA mRNA,and the expression levels of mTOR and p-mTOR proteins in the cells in OAD group were all decreased(P<0.05);compared with OAD group,the TG level,the expression levels of FASN and ACACA mRNA,and the expression levels of mTOR and p-mTOR proteins in the cells in OAM group were all increased(P<0.05).Conclusion:ANGPTL6 can improve MCD diet-induced liver lipid accumulation in the mice,and its mechanism may be related to the inhibition of mTOR signaling pathway activity.关键词
血管生成素样蛋白6/代谢相关脂肪性肝病/哺乳动物雷帕霉素靶蛋白/脂质代谢/小鼠,C57BL/6Key words
Angiopoietin-like protein 6/Metabolic dysfunction-associated fatty liver disease/Mammalian target of rapamycin/Lipid metabolism/Mice,C57BL/6分类
医药卫生引用本文复制引用
温升聪,邓娅娅,张鑫铬,何佳怡,孙雨萌,朱井玲,宋永顺,张云华..血管生成素样蛋白6对蛋氨酸和胆碱缺乏饮食诱导的小鼠肝脏脂质沉积的改善作用及其机制[J].吉林大学学报（医学版）,2026,52(4):905-913,9.基金项目
国家自然科学基金项目(82260126,32460221) （82260126,32460221）
兵团指导性科技计划项目(2024ZD020) （2024ZD020）
新疆第二医学院科研项目(ZR202540) （ZR202540）
