Estrogen signaling and the Metabolic Syndrome: Targeting the hepatic ERalpha action

We have previously shown that total estrogen receptor alpha (ERalpha knockout (KO) mice exhibit hepatic insulin resistance. To investigate the contribution of hepatic ERalpha action for the observed phenotype, we established a liver-selective ERalphaKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERalpha selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ERalpha action may not be the initiating factor for the previously identified hepatic insulin resistance in ERalphaKO mice. We have previously shown that total estrogen receptor alpha (ERalpha knockout (KO) mice exhibit hepatic insulin resistance. To investigate the contribution of hepatic ERalpha action for the observed phenotype, we established a liver-selective ERalphaKO mouse model, LERKO. Using microarray analysis, we compared the hepatic transcriptional profile of LERKO vs control mice.我们此前已证实，全身雌激素受体α（estrogen receptor alpha, ERα）敲除（knockout, KO）小鼠可表现出肝脏胰岛素抵抗。为探究肝脏ERα的作用在该观测表型中的贡献，我们构建了肝脏选择性ERα敲除小鼠模型（LERKO）。本研究证实，LERKO小鼠可在肝脏中特异性高效下调ERα的表达水平。然而，LERKO小鼠与野生型对照小鼠的体重无显著差异；即便经高脂膳食（high fat diet）挑战后，二者的激素谱、胰岛素及葡萄糖应答水平也均无明显差别。此外，LERKO小鼠的肝脏转录组谱仅存在极细微的变化。综上，本研究结果表明，肝脏ERα的作用可能并非ERα全身敲除小鼠中此前所发现的肝脏胰岛素抵抗的起始诱因。我们此前已证实，全身雌激素受体α（estrogen receptor alpha, ERα）敲除（knockout, KO）小鼠可表现出肝脏胰岛素抵抗。为探究肝脏ERα的作用在该观测表型中的贡献，我们构建了肝脏选择性ERα敲除小鼠模型（LERKO）。我们通过基因芯片分析（microarray analysis）比较了LERKO小鼠与对照小鼠的肝脏转录组谱。