Effects of periodic maternal separation on fat mass of rat offspring in adulthood vary with the separation timing, during either light or dark phase
Effects of periodic maternal separation on fat mass of rat offspring in adulthood vary with the separation timing, during either light or dark phase
复制标题
定期母体分离对成年大鼠后代脂肪量的影响随分离时间的不同而变化，无论是在亮期还是在暗期
DOI：
10.1111/cga.12089
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Fukui Y
中科院分区：
文献类型：
--
作者：
Sawada N;Sakata-Haga H;Fukui Y
非最佳胎儿环境导致的低出生体重在流行病学上与成人疾病的风险较高相关，并且也已使用母体营养不良的动物模型进行了证明。在这项研究中，我们对怀孕的小鼠进行了50%的食物限制（FR），并使用胎肝对基因表达和启动子DNA甲基化进行了全基因组分析。食物限制的效果在出生前后是相反的，这一事实鼓励我们使用母体肝脏寻找与成人卡路里限制（CR）相反表达的基因。在相反的调控基因，我们确定trib1（tribbles同源1）。使用转基因小鼠，trib1已被证明对高脂血症和胰岛素抵抗的风险有明显的贡献。我们的数据表明thetrib1的表达及其启动子DNA甲基化可以受到生理影响（通过母体营养），因此可能是成人疾病发育起源的强有力的候选基因。此外，lepr（瘦素受体）基因下调母亲FR，表明其在诱导肥胖和糖尿病的潜在作用。基因表达以及启动子DNA甲基化分析显示，糖皮质激素受体靶基因受母体FR的调控，这支持了先前的研究，即胎儿糖皮质激素暴露在疾病的发育起源机制中具有重要作用。我们的转录组学分析数据还表明，母体FR损害了免疫系统的发育。在这项研究中，负责健康和疾病的发展起源的候选基因清单和讨论。
Low birthweight resulting from a non‐optimal fetal environment is correlated epidemiologically to a higher risk of adult diseases, and which has also been demonstrated using animal models for maternal undernutrition. In this study, we subjected pregnant mice to 50% food restriction (FR), and profiled gene expression and promoter DNA methylation genome‐wide using the fetal livers. The fact that effect of food restriction is opposite between before and after birth encouraged us to hunt for genes that are expressed oppositely to adult calorie restriction (CR) using the maternal livers. Among oppositely regulated genes, we identifiedtrib1(tribbles homolog 1). Using genetically modified mice,trib1has been shown to have a demonstrable contribution to a risk of hypertriglyceridaemia and insulin resistance. Our data showed that thetrib1expression and its promoter DNA methylation could be affected physiologically (by maternal nutrition), and therefore might be a strong candidate gene for developmental origins of adult diseases. Furthermore,lepr(leptin receptor) gene was downregulated by maternal FR, indicating its potential role in induction of obesity and diabetes. Gene expression as well as promoter DNA methylation profiling revealed that glucocorticoid receptor target genes were regulated by maternal FR. This supports previous studies that suggest an important role of fetal glucocorticoid exposure in the mechanism of developmental origins of diseases. Our transcriptomics profiling data also suggested that maternal FR impaired development of the immune system. An inventory of candidate genes responsible for developmental origins of health and disease is presented and discussed in this study.