MATERNAL DIET MODIFIES THE FETAL PRIMATE EPIGENOME AND CIRCADIAN GENE EXPRESSION

母亲饮食改变胎儿灵长类表观基因组和昼夜节律基因表达

基本信息

  • 批准号:
    8357765
  • 负责人:
  • 金额:
    $ 5.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-05-01 至 2012-04-30
  • 项目状态:
    已结题

项目摘要

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.
这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的, 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量, 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 根据Barker的胎儿起源成人疾病假说,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中的表观遗传变化对基因表达进行重编程而发生的。在啮齿动物中进行的研究清楚地表明,许多母体操作可导致发育中胎儿的表观遗传修饰,从而导致体重稳态的长期改变。令人惊讶的是,一直缺乏研究是否修改母体膳食脂肪会导致类似的表观遗传修饰的胎儿后代。此外,没有证据表明表观遗传修饰是否发生在灵长类动物物种中。这项建议的一般假设是,怀孕期间和新生儿早期的饮食和代谢健康对儿童代谢疾病的发展有重大影响。该建议的重点是母亲的高脂肪饮食对胎儿和出生后的表观遗传特征的昼夜节律基因在肝脏和下丘脑的NHP的影响。在这些研究中,肝脏和下丘脑的样品取自对照饮食或高脂肪饮食动物的后代。将表征染色质结构、组蛋白修饰(组蛋白乙酰化/甲基化)的变化以及表观遗传修饰基因表达的变化。这些研究的一个特别重点是表征能量稳态的昼夜节律调节的变化。这些研究将提供关键的洞察力的潜在机制,母亲的营养操纵可能会导致长期的风险代谢疾病的后代。

项目成果

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KEVIN L GROVE其他文献

KEVIN L GROVE的其他文献

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{{ truncateString('KEVIN L GROVE', 18)}}的其他基金

PROJECT 1: METABOLIC AND NEUROENDOCRINE RESPONSES TO ANDROGEN AND DIET
项目 1:雄激素和饮食的代谢和神经内分泌反应
  • 批准号:
    8510085
  • 财政年份:
    2013
  • 资助金额:
    $ 5.82万
  • 项目类别:
MATERNAL HIGH FAT DIET AND THE MELANOCORTIN SYSTEM IN THE OFFSPRING
母亲的高脂肪饮食和后代的黑皮质素系统
  • 批准号:
    8357879
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
GESTATIONAL DIABETES LEADS TO CARDIOVASCULAR VULNERABILITY IN OFFSPRING
妊娠期糖尿病导致后代心血管脆弱
  • 批准号:
    8357786
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
TREATMENT OF OBESITY AND INSULIN RESISTANCE IN THE NON-HUMAN PRIMATE
非人类灵长类动物肥胖和胰岛素抵抗的治疗
  • 批准号:
    8357811
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
ACTIONS OF MELANOCORTIN AGONISTS IN OBESE PRIMATES
黑皮质素激动剂对肥胖灵长类动物的作用
  • 批准号:
    8357859
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
Molecular mechanisms underlying NHP pancreatic beta cell failure, and recovery
NHP 胰腺 β 细胞衰竭和恢复的分子机制
  • 批准号:
    8214751
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
THE EFFECT OF HUMANIZED ANTIBODIES TO ANGPTL4 ON TRIGLYERIDES & VLDL-LEVELS
ANGPTL4 人源化抗体对甘油三酯的影响
  • 批准号:
    8357857
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
MECHANISMS FOR FETAL HEPATIC PROGRAMMING IN THE NON-HUMAN PRIMATE
非人灵长类动物胎儿肝脏编程机制
  • 批准号:
    8357764
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
NEUROENDOCRINE RESPONSE TO GASTRIC BYPASS IN NONHUMAN PRIMATES
非人类灵长类动物胃绕道的神经内分泌反应
  • 批准号:
    8357861
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:
HIGH FAT DIET INDUCED ALTERATIONS IN GENE EXPRESSION IN THE NONHUMAN PRIMATE
高脂肪饮食引起非人类灵长类动物基因表达的改变
  • 批准号:
    8357812
  • 财政年份:
    2011
  • 资助金额:
    $ 5.82万
  • 项目类别:

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