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榄香素诱发小鼠脂质代谢紊乱的分子机制探讨

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目的 探讨榄香素(elemicin,Ele)诱导小鼠脂质代谢异常的潜在机制.方法 采用200 mg/kg Ele对小鼠进行灌胃处理28 d,基于非靶代谢组学分析筛选血清差异代谢物;通过实时定量聚合酶链式反应(qPCR)检测肝脏、肠组织中相关代谢酶的基因表达情况.结果 Ele暴露可扰乱甘油磷脂代谢通路、亚油酸代谢通路和叶酸一碳池,使小鼠血清中二十二烷六烯酰基肉碱(cervonyl carnitine)、磷酸胆碱(phosphorylcholine)和 16-羟基棕榈酸(16-Hydroxyhexadecanoic acid)分别降低至对照组的 47%、71%、32%.Ele 暴露显著上调肝脏 Slc22a5、Cyp4a12a、Cyp4a12b 的基因表达,抑制十二指肠 Slc22a5、Slc25a20、Chkb 基因表达,上调回肠中Chkb和结肠Slc22a5、Slc25a20基因表达,抑制结肠Enpp7基因表达(t=2.494~4.575,P值均<0.05).结论 Ele暴露可调节脂质代谢相关基因表达,扰乱甘油磷脂代谢、亚油酸代谢和叶酸一碳池通路,诱发小鼠脂质代谢异常.
Molecular mechanisms of elemicin-induced lipid metabolism disorders in mice
Objective To investigate the underlying mechanisms of elemicin-induced lipid metabolism disorders in mice.Methods Mice were orally administered with elemicin at a dose of 200 mg/kg for 28 days,and serum differentially expressed metabo-lites were screened using non-target metabolomics analysis.The expression of related metabolic enzymes was detected in mouse liver and intestine specimens using quantitative real-time PCR(qPCR)assay.Results Elemicin treatment affected glycerol phospholipid,lino-leic acid and folic acid-carbon metabolism pathways,and caused serum cervonyl carnitine,phosphorylcholine and 16-hydroxyhexade-canoic acid reductions by 47%,71%and 32%in mice relative to controls.Elemicin treatment significantly up-regulated Slc22a5,Cyp4al2a and Cyp4al2b gene expression in mouse livers,Chkb gene expression in mouse ilea and Slc22a5 and Slc25a20 gene expres-sion in mouse colons,and suppressed Slc22a5,Slc25a20 and Chkbgene expression in mouse duodenums and Enpp7 gene expression in mouse colons(t=2.494 to 4.575,all P values<0.05).Conclusions Elemicin treatment may induce lipid metabolism disorders in mice through mediatinglipid metabolism-associated gene expression and affecting glycerol phospholipid,linoleic acid and folic acid-car-bon metabolism pathways.

MouseElemicinLipid metabolismMetabolomicsGene expression

李弈、白逸飞、张逸、张展

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南方医科大学,广东广州 510515

南京医科大学

小鼠 榄香素 脂质代谢 代谢组学 基因表达

2024

江苏预防医学
江苏省疾病预防控制中心 江苏省预防医学会

江苏预防医学

影响因子:1.319
ISSN:1006-9070
年,卷(期):2024.35(4)