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Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis

机译:脂联素及其受体在脂肪性肝病和肝硬化的啮齿动物模型中的作用

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摘要

AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA.RESULTS: Systemic adiponectin is reduced in fat-fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice.CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.
机译:目的:测定脂肪性肝病或肝硬化啮齿类动物体内的循环脂联素和肝脂联素,研究脂联素受体AdipoR1在mRNA和蛋白质水平上的表达以及AdipoR2在mRNA水平上的表达。方法:以脂肪喂养的大鼠为模型肝病和小鼠胆管结扎以研究肝硬化肝。通过实时RT-PCR确定AdipoR1和AdipoR2 mRNA的表达。通过免疫印迹分析AdipoR1蛋白。结果:脂肪喂养的大鼠体内脂联素水平降低,而胆管结扎(BDL)后小鼠体内的脂联素水平升高。与对照组相比,脂肪样肝中的肝脂联素蛋白较低,但在BDL小鼠的肝中则没有。在人肝样品或原代人肝细胞或大鼠肝脏中均未检测到脂联素mRNA,但重组脂联素被离体的肝细胞体外吸收。在对照组和喂食动物的肝脏组织中,AdipoR1 mRNA和AdipoR1蛋白水平相似,而AdipoR2 mRNA被诱导。结论:我们的研究表明,在脂肪性肝病的大鼠模型中,循环脂联素减少,而在肝硬化小鼠模型中,循环脂联素升高,并且已经描述了类似的发现在人类中。脂联素受体的肝表达降低仅在肝硬化中发现。

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