MATERNAL DIET MODIFIES THE FETAL PRIMATE EPIGENOME AND CIRCADIAN GENE EXPRESSION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 根据巴克的成人疾病胎儿起源假说，妊娠环境的扰动影响成人疾病的发展。这是通过染色质结构的表观遗传变化重新编程基因表达来实现的。在啮齿动物身上所做的研究清楚地表明，许多母体操作可以在发育中的胎儿中引起表观遗传改变，从而导致体重动态平衡的长期改变。令人惊讶的是，关于修改母体饮食脂肪是否会在胎儿后代中引起类似的表观遗传修改的研究一直缺乏。此外，还没有证据表明灵长类物种是否发生了表观遗传修饰。这一建议的一般假设是，孕期和新生儿早期的饮食和代谢健康对儿童代谢性疾病的发展有重大贡献。这项建议侧重于母亲高脂肪饮食对NHP胎儿和出生后肝脏和下丘脑昼夜节律基因表观遗传特征的影响。在这些研究中，肝脏和下丘脑的样本来自于保持对照饮食或高脂肪饮食的动物的后代。将描述染色质结构的变化、组蛋白修饰(组蛋白乙酰化/甲基化)以及经过表观遗传修饰的基因表达的变化。这些研究的一个特别的焦点是描述能量平衡的昼夜节律的变化。这些研究将为母体营养控制可能导致子代代谢性疾病的长期风险的潜在机制提供关键的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. According to the Barker's Fetal Origins of Adult Disease Hypothesis, perturbations in the gestational milieu influence the development of adult diseases. This occurs through the reprogramming of gene expression via epigenetic changes in chromatin structure. It is clear from studies done in rodents that numerous maternal manipulations can cause epigenetic modifications in the developing fetus that results in long-term modification of body weight homeostasis. Surprisingly, there has been a lack of study of whether modification of maternal dietary fat can cause similar epigenetic modifications in the fetal offspring. Furthermore, there has been no evidence of whether epigenetic modifications occur in primate species. The general hypothesis of this proposal is that diet and metabolic health during pregnancy and the early neonatal period significantly contribute to the development of metabolic diseases in children. This proposal focuses upon the effects of a maternal high fat diet upon the fetal and postnatal epigenetic characteristics of circadian genes in the liver and hypothalamus of the NHP. For these studies liver and hypothalamic are obtained samples from offspring of animals maintained either on a control diet or a high fat diet. Changes in chromatin structure, histone modifications (histone acetylation/methylation) as well as changes in expression of genes that are epigenetically modified will be characterized. A special focus of these studies is to characterize changes in circadian regulation of energy homeostasis. These studies will provide critical insight into the underlying mechanism by which maternal nutritional manipulations can cause long-term risks of metabolic diseases in offspring.