Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways
Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways
复制标题
产前摄入咖啡因导致胎鼠代谢组改变，可能是由于循环糖皮质激素水平增加以及外周葡萄糖和脂质代谢途径改变所致
DOI：
10.1016/j.taap.2012.05.002
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发表时间：
2012-07-15
影响因子：
3.8
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Yansong;Xu, Dan;Wang, Hui
本研究的目的是阐明产前摄入咖啡因后胎鼠代谢组的变化，并探讨与胎儿循环糖皮质激素（GC）增加相关的潜在机制。妊娠 Wistar 大鼠从妊娠第 11 天至第 20 天每天灌胃不同剂量的咖啡因（0、20、60 和 180 mg/kg）。通过基于 H-1 核磁共振的代谢组学分析 GD20 时胎儿血浆和羊水的代谢组。通过实时RT-PCR和免疫组织化学检测胎儿肝脏和腓肠肌中GC代谢、葡萄糖和脂质代谢途径涉及的基因和蛋白表达。咖啡因显着改变胎儿血浆代谢组，表现为α-和β-葡萄糖升高、多种脂质含量降低、载脂蛋白含量变化以及多种氨基酸水平升高。羊水的代谢组显示出与胎儿血浆相似的变化。此外，胎儿肝脏和腓肠肌中11β-羟基类固醇脱氢酶2（11β-HSD-2）的表达降低，而血液GC水平以及11β-HSD-1和糖皮质激素受体（GR）的表达升高。同时，咖啡因治疗后胰岛素样生长因子1（IGF-1）、IGF-1受体和胰岛素受体的表达下降，而脂联素受体2、瘦素受体和AMP激活蛋白激酶α2的表达增加。产前摄入咖啡因会改变胎儿代谢组，这可能是由于循环GC增加、GC代谢激活和外周代谢组织GR表达增强而引起的葡萄糖和脂质代谢途径的改变。 (C) 2012 Elsevier Inc. 保留所有权利。
The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by H-1 nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated alpha- and beta-glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11 beta-hydroxysteroid dehydrogenase 2 (11 beta-HSD-2) were decreased, while the level of blood GC and the expressions of 11 beta-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase alpha 2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. (C) 2012 Elsevier Inc. All rights reserved.