Neumeier Markus, Hellerbrand Claus, Gäbele Erwin, Buettner Roland, Bollheimer Cornelius, Weigert Johanna, Schäffler Andreas, Weiss Thomas S, Lichtenauer Monika, Schölmerich Jurgen, Buechler Christa
Department of Internal Medicine I, University of Regensburg, Regensburg D-93042, Germany.
World J Gastroenterol. 2006 Sep 14;12(34):5490-4. doi: 10.3748/wjg.v12.i34.5490.
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.
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.
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.
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.
测定患有脂肪性肝病或肝硬化的啮齿动物体内循环和肝脏中的脂联素,并在mRNA和蛋白质水平上研究脂联素受体AdipoR1以及在mRNA水平上研究脂联素受体AdipoR2的表达。
用高脂喂养的大鼠作为脂肪性肝病模型,用小鼠胆管结扎术研究肝硬化肝脏。通过实时逆转录聚合酶链反应(RT-PCR)测定AdipoR1和AdipoR2 mRNA的表达。通过免疫印迹分析AdipoR1蛋白。用酶联免疫吸附测定法(ELISA)测量脂联素。
高脂喂养的大鼠体内循环脂联素减少,但胆管结扎(BDL)后的小鼠体内循环脂联素升高。与对照组相比,脂肪变性肝脏中肝脏脂联素蛋白含量较低,但BDL小鼠的肝脏中肝脏脂联素蛋白含量并未降低。在人类肝脏样本或原代人肝细胞以及大鼠肝脏中均未检测到脂联素mRNA,但重组脂联素在体外可被分离的肝细胞摄取。在对照动物和高脂喂养动物的肝脏组织中,AdipoR1 mRNA和AdipoR1蛋白水平相似,而AdipoR2 mRNA被诱导表达。在BDL小鼠的肝脏中,AdipoR2 mRNA以及AdipoR1 mRNA和蛋白均受到抑制。
我们的研究表明,在脂肪性肝病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,并且在人类中也有类似的发现。仅在肝硬化中发现脂联素受体的肝脏表达减少。