PDF(Pubmed)
Abstract：
We have previously demonstrated that the glucocorticoid receptor β (GRβ) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRβ isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRβ regulates lipids that cause metabolic dysfunction. To determine the effect of GRβ on hepatic lipid classes and molecular species, we overexpressed GRβ (GRβ-Ad) and vector (Vec-Ad) using adenovirus delivery, as we previously described. We fed the mice a normal chow diet for 5 days and harvested the livers. We utilized liquid chromatography-mass spectrometry (LC-MS) analyses of the livers to determine the lipid species driven by GRβ. The most significant changes in the lipidome were monoacylglycerides and cholesterol esters. There was also increased gene expression in the GRβ-Ad mice for lipogenesis, eicosanoid synthesis, and inflammatory pathways. These indicate that GRβ-induced glucocorticoid resistance may drive hepatic fat accumulation, providing new therapeutic advantages.
摘要：
我们先前已经证明，糖皮质激素受体β（GRβ）同工型在饲喂正常饮食的小鼠中诱导肝性脂肪变性。GRβ亚型抑制糖皮质激素结合亚型GRα，降低反应性和诱导糖皮质激素抵抗。我们假设GRβ调节引起代谢功能障碍的脂质。为了确定GRβ对肝脏脂质类别和分子种类的影响，我们使用腺病毒递送过表达GRβ（GRβ-Ad）和载体（Vec-Ad），正如我们之前所描述的。我们给小鼠喂食正常的食物饮食5天并收获肝脏。我们利用肝脏的液相色谱-质谱（LC-MS）分析来确定由GRβ驱动的脂质种类。脂质组中最重要的变化是单酰基甘油酯和胆固醇酯。在GRβ-Ad小鼠中脂肪生成的基因表达也增加，类花生酸合成，和炎症途径。这些表明GRβ诱导的糖皮质激素抵抗可能驱动肝脏脂肪积累，提供新的治疗优势。
