Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Department of Obstetrics and Gynecology, Okayama, Japan.
Mol Cell Endocrinol. 2012 Jan 2;348(1):120-7. doi: 10.1016/j.mce.2011.07.047. Epub 2011 Aug 4.
Constitutive androstane receptor (CAR) has been reported to decrease insulin resistance, while obesity and insulin resistance may also be involved in the pathogenesis of preeclampsia. We examined whether a CAR ligand, 1,4-bis(2-(3,5-dichloropyridyloxy)) benzene (TCPOBOP), can ameliorate the signs of preeclampsia in high-fat diet (HFD)-induced obese pregnant mice to examine a possibility of CAR as a therapeutic target. We employed six groups including non-pregnant, HFD-fed or control diet-fed pregnant mice with or without TCPOBOP treatment (n=6). In HFD pregnant mice, insulin resistance increased with increasing expression of gluconeogenic and lipogenic genes and abnormal adipocytokine levels. TCPOBOP treatment, which was once-weekly intraperitoneal injections (0.5 mg/kg) and started at day 0.5 of pregnancy, improved glucose tolerance with significant changes of gluconeogenic, lipogenic and adipocytokine genes. HFD pregnant mice had hypertension and proteinuria, while TCPOBOP treatment ameliorated these signs. Our data suggested CAR might be a potential therapeutic target for obese preeclampsia patients with insulin resistance.
组成型雄烷受体（CAR）已被报道可降低胰岛素抵抗，而肥胖和胰岛素抵抗也可能参与子痫前期的发病机制。我们研究了 CAR 配体 1,4-双（2-（3,5-二氯吡啶氧基））苯（TCPOBOP）是否可以改善高脂肪饮食（HFD）诱导的肥胖妊娠小鼠的子痫前期症状，以检验 CAR 作为治疗靶点的可能性。我们使用了包括非妊娠、HFD 喂养或对照饮食喂养的怀孕小鼠以及用或不用 TCPOBOP 处理的怀孕小鼠六组（每组 n=6）。在 HFD 妊娠小鼠中，胰岛素抵抗随着糖异生和脂肪生成基因的表达增加以及异常脂肪细胞因子水平而增加。TCPOBOP 处理，每周一次腹腔注射（0.5mg/kg），从妊娠第 0.5 天开始，改善了葡萄糖耐量，糖异生、脂肪生成和脂肪细胞因子基因发生显著变化。HFD 妊娠小鼠有高血压和蛋白尿，而 TCPOBOP 治疗改善了这些症状。我们的数据表明，CAR 可能是肥胖合并胰岛素抵抗的子痫前期患者的潜在治疗靶点。
