Multigenerational epigenetic programming induced by paternal obesity and prediabetes

父亲肥胖和糖尿病前期诱导的多代表观遗传编程

基本信息

项目摘要

“Multigenerational epigenetic programming induced by paternal obesity and prediabetes” ABSTRACT Obesity and its related co-morbidities have reached epidemic proportions in the United States and other developed countries, posing an unprecedented challenge to health services. We find that a single generation of paternal obesity and prediabetes programs male offspring with a latent metabolic defect that is exposed by overnutrition. The latent phenotype is transmitted paternally for two generations without further exposure to paternal obesity. Paternal transmission is associated with changes in the sperm small RNAs that are predicted to regulate transcriptional processes. This non-genetic transmission of phenotypes across generations may be a significant contributor to the risk of obesity, and may require intervention and prevention measures across multiple generations. Understanding the scope and the mechanism of this heritable epigenetic programming phenomenon will be critical in developing new strategies to manage or prevent the effects of paternal obesity. This study has the potential to identify biomarkers that could be used to characterize the syndrome in humans. We propose to determine (1) if multiple generations of exposure to paternal obesity and prediabetes amplify the metabolic phenotype in subsequent generations, and/or increase its heritability; (2) the mechanism of paternal inheritance of the metabolic phenotype, through epigenetic changes in the sperm of affected sires; (3) the transcriptional changes that occur in the early embryo in response to epigenetic changes in the sperm. The concept that environmental exposures can induce heritable epigenetic states has received much recent attention, but the subject is very poorly understood and documented. Our experimental system permits a direct test of the epigenetic inheritance model: genetic variants can be ruled out as a factor in transmission because we study isogenic mice, transmission through the paternal line rules out in utero metabolic exposure as a cause, and the high penetrance of the metabolic phenotype makes it amenable to mechanistic studies. The unexpected multigenerational effect of paternal obesity/prediabetes on the metabolism of genetically identical offspring challenges established views on the causes of obesity. This study will provide evidence that there is an inborn but non-genetic component to the risk of obesity, insights into the mechanisms by which that risk is created and transmitted, and a system amenable to further study of the phenomenon.
“父亲肥胖和糖尿病前期诱导的多代表观遗传编程” 抽象的 肥胖及其相关并发症在美国和其他国家已达到流行病的程度 发达国家的卫生服务面临前所未有的挑战。我们发现单一代 父亲肥胖和糖尿病前期的研究表明,男性后代存在潜在的代谢缺陷,而这种缺陷是通过以下方式暴露出来的: 营养过剩。潜伏表型通过父系遗传两代,无需进一步暴露 父亲肥胖。父本遗传与预测的精子小 RNA 的变化有关 调节转录过程。这种表型跨代的非遗传传递可能是 是导致肥胖风险的一个重要因素,可能需要采取全面的干预和预防措施 多代。了解这种可遗传的表观遗传编程的范围和机制 这种现象对于制定控制或预防父亲肥胖影响的新策略至关重要。 这项研究有可能确定可用于表征人类综合症的生物标志物。 我们建议确定(1)多代人暴露于父亲肥胖和糖尿病前期是否会加剧 后代的代谢表型,和/或增加其遗传力; (2) 机理 通过受影响公牛精子的表观遗传变化,代谢表型的父系遗传; (3) 早期胚胎中因精子表观遗传变化而发生的转录变化。 环境暴露可以诱导可遗传的表观遗传状态的概念最近得到了广泛的关注。 关注,但对该主题的理解和记录却很少。我们的实验系统允许直接 表观遗传模型的测试:可以排除遗传变异作为传播因素,因为 我们研究同基因小鼠,通过父系传播排除了子宫内代谢暴露作为 原因,并且代谢表型的高外显率使其适合机制研究。 父亲肥胖/糖尿病前期对遗传代谢的意想不到的多代影响 相同的后代挑战了关于肥胖原因的既定观点。这项研究将提供证据表明 肥胖风险存在先天但非遗传因素,深入了解该因素的机制 风险被创造和传播,并且系统适合进一步研究这种现象。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DARIO BOFFELLI其他文献

DARIO BOFFELLI的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('DARIO BOFFELLI', 18)}}的其他基金

Multigenerational epigenetic programming induced by paternal obesity and prediabetes
父亲肥胖和糖尿病前期诱导的多代表观遗传编程
  • 批准号:
    10424713
  • 财政年份:
    2016
  • 资助金额:
    $ 55.74万
  • 项目类别:
Multigenerational epigenetic programming induced by paternal obesity and prediabetes
父亲肥胖和糖尿病前期诱导的多代表观遗传编程
  • 批准号:
    9977169
  • 财政年份:
    2016
  • 资助金额:
    $ 55.74万
  • 项目类别:
Transgenerational epigenetic effects induced by paternal preconception ethanol
父本孕前乙醇诱导的跨代表观遗传效应
  • 批准号:
    8624580
  • 财政年份:
    2014
  • 资助金额:
    $ 55.74万
  • 项目类别:
Heritability of gene expression variants in isogenic mice
等基因小鼠基因表达变异的遗传力
  • 批准号:
    8588711
  • 财政年份:
    2013
  • 资助金额:
    $ 55.74万
  • 项目类别:
Identification of Primate-Specific Regulatory Elements of Cholesterol Homeostasis
灵长类动物特异性胆固醇稳态调节元件的鉴定
  • 批准号:
    7589777
  • 财政年份:
    2007
  • 资助金额:
    $ 55.74万
  • 项目类别:
Identification of Primate-Specific Regulatory Elements of Cholesterol Homeostasis
灵长类动物特异性胆固醇稳态调节元件的鉴定
  • 批准号:
    7195980
  • 财政年份:
    2007
  • 资助金额:
    $ 55.74万
  • 项目类别:
Identification of Primate-Specific Regulatory Elements of Cholesterol Homeostasis
灵长类动物特异性胆固醇稳态调节元件的鉴定
  • 批准号:
    7393163
  • 财政年份:
    2007
  • 资助金额:
    $ 55.74万
  • 项目类别:
Identification of Primate-Specific Regulatory Elements of Cholesterol Homeostasis
灵长类动物特异性胆固醇稳态调节元件的鉴定
  • 批准号:
    7799857
  • 财政年份:
    2007
  • 资助金额:
    $ 55.74万
  • 项目类别:

相似海外基金

Understanding early causal pathways in ADHD: can early-emerging atypicalities in activity and affect cause later-emerging difficulties in attention?
了解 ADHD 的早期因果路径:早期出现的活动和影响的非典型性是否会导致后来出现的注意力困难?
  • 批准号:
    MR/X021998/1
  • 财政年份:
    2023
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Research Grant
Predictive information and cognitive process: How affect the emotional value of pre-cue on the attention control process
预测信息与认知过程:预提示的情感价值如何影响注意控制过程
  • 批准号:
    22K03209
  • 财政年份:
    2022
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Visuocortical Dynamics of Affect-Biased Attention in the Development of Adolescent Depression
青少年抑郁症发展过程中情感偏向注意力的视觉皮层动力学
  • 批准号:
    10380686
  • 财政年份:
    2019
  • 资助金额:
    $ 55.74万
  • 项目类别:
Spatial and Temporal Mechanisms of Affect-Biased Attention
情感偏向注意力的时空机制
  • 批准号:
    RGPIN-2014-04202
  • 财政年份:
    2019
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Discovery Grants Program - Individual
Visuocortical Dynamics of Affect-Biased Attention in the Development of Adolescent Depression
青少年抑郁症发展过程中情感偏向注意力的视觉皮层动力学
  • 批准号:
    9888437
  • 财政年份:
    2019
  • 资助金额:
    $ 55.74万
  • 项目类别:
Visuocortical Dynamics of Affect-Biased Attention in the Development of Adolescent Depression
青少年抑郁症发展过程中情感偏向注意力的视觉皮层动力学
  • 批准号:
    10597082
  • 财政年份:
    2019
  • 资助金额:
    $ 55.74万
  • 项目类别:
Spatial and Temporal Mechanisms of Affect-Biased Attention
情感偏向注意力的时空机制
  • 批准号:
    RGPIN-2014-04202
  • 财政年份:
    2018
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Discovery Grants Program - Individual
Spatial and Temporal Mechanisms of Affect-Biased Attention
情感偏向注意力的时空机制
  • 批准号:
    RGPIN-2014-04202
  • 财政年份:
    2017
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Discovery Grants Program - Individual
Emerging relations between attention and negative affect in the first two years of life
生命头两年注意力与负面情绪之间的新关系
  • 批准号:
    9673285
  • 财政年份:
    2016
  • 资助金额:
    $ 55.74万
  • 项目类别:
Spatial and Temporal Mechanisms of Affect-Biased Attention
情感偏向注意力的时空机制
  • 批准号:
    RGPIN-2014-04202
  • 财政年份:
    2016
  • 资助金额:
    $ 55.74万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了