Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.
Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.
复制标题
脂联素缺乏损害母鼠对妊娠的代谢适应。
作者：
Qiao L;Wattez JS;Lee S;Nguyen A;Schaack J;Hay WW Jr;Shao J
妊娠期糖尿病（GDM）患者普遍存在低脂联素血症。为了研究低脂联素血症在GDM中的因果作用，将脂联素基因敲除（Adipoq−/−）和野生型（WT）小鼠杂交，以产生有或没有脂联素缺乏的妊娠小鼠模型。腺病毒载体介导的体内转导用于在晚期妊娠期间重建脂联素。结果表明，Adipoq−/−母鼠在妊娠后期出现葡萄糖耐受不良和高脂血症。在Adipoq−/−母鼠中检测到胎仔体重增加。脂联素重建消除了Adipoq−/−母鼠的这些代谢缺陷。Adipoq−/−母鼠的肝脏葡萄糖和甘油三酯生成率显著高于WT母鼠。在Adipoq−/−母鼠的性腺脂肪中发现了强烈增强的脂解作用。有趣的是，在Adipoq−/−和WT母鼠的代谢活性组织中，胰岛素诱导的葡萄糖处置和胰岛素信号传导水平相似，表明母体脂联素缺乏不会降低胰岛素敏感性。然而，在Adipoq−/−母鼠中观察到血清胰岛素浓度显著降低。此外，与WT母鼠相比，Adipoq−/−母鼠的β细胞质量显著降低，但葡萄糖刺激的胰岛素释放没有显著降低。总之，这些结果表明，脂联素在控制母体代谢适应妊娠中起着重要作用。
Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq−/−) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector–mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq−/− dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq−/− dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq−/− dams. Hepatic glucose and triglyceride production rates of Adipoq−/− dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq−/− dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq−/− and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq−/− dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq−/− dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.