两种抗雌激素药物对雌性斑马鱼脂肪代谢的影响

EFFECTS OF TWO ANTI-ESTROGEN DRUGS EXPOSURE ON LIPID METABOLISM OF FEMALE ZEBRAFISH (DANIO RERIO)

  • 摘要: 为探究雌激素对雌鱼体内脂肪代谢的影响,研究分别使用50和250 μg/L的来曲唑(Letrozole、LET)与他莫昔芬(Tamoxifen、TAM)两种抗雌激素药物,构建了雌性斑马鱼(Danio rerio)雌激素缺乏模型和雌激素受体竞争抑制模型,并检测两种药物处理后斑马鱼肝脏、内脏和肌肉的甘油三酯(TG)含量变化以及肝脏内雌激素和脂肪代谢相关基因的变化。结果显示,低浓度LET处理后雌鱼肝脏和内脏TG显著上升(P < 0.05);高浓度TAM处理后肝脏TG含量显著降低(P < 0.05),其他各组处理TG均无差异。基因mRNA检测结果表明,两种浓度LET和TAM处理的雌性斑马鱼芳香化酶(CYP19A)表达均显著下调(P < 0.05),低浓度TAM暴露导致雌激素受体(ERα)表达显著下调(P < 0.05)。此外,两种浓度LET处理均引起了脂肪酸合成酶(FAS)表达显著上调,微粒体的TG转运蛋白(MTP)表达显著下调(P < 0.05);低浓度TAM引起了MTP表达显著下调(P < 0.05),而高浓度TAM组则引起了MTP表达显著上调(P < 0.05)。综合各相关指标,研究结果表明雌激素确实在雌性斑马鱼脂肪代谢中发挥作用,然而不同程度和方式的雌激素抑制会导致不同的脂代谢失调表现,这提示鱼体内雌激素紊乱所导致的脂代谢失调与雌激素浓度和作用通路上的受阻位点有关,并受到多重因子参与的内分泌调控网络的调节。

     

    Abstract: In higher animals, estrogen can regulate lipid metabolism of females; however, whether estrogen regulates fish lipid metabolism is unclear. To explore effects of estrogen on lipid metabolism in zebrafish, letrozole (LET) and tamoxifen (TAM) were treated female zebrafish (0.14±0.01) g for 5 weeks to measure triglyceride (TG) concentrations in liver, visceral and muscle and the expressions of the hepatic genes related to estrogen and lipid metabolism. The results showed that low dose LET significantly increased TG in liver and viscera but not in muscle. Low dose TAM did not impact No TG content in all tested tissues but high dose TAM significantly decreased liver TAG. LET and TAM significantly induced CYP19A mRNA, and low dose TAM decreased ERα. LET increased FAS but decreased MTP expression. DGAT had an increase tendency, and CPT-1 and PPARα had a decreased tendency. It suggests a dyslipi-demia symptom in the LET exposure groups. Low dose TAM reduced MTP and high dose TAM enhanced it (P < 0.05). These results showed important role of estrogen in lipid metabolism in female zebrafish with a complex dosageand tissue-dependent pattern.

     

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