Epigenetic regulation of gene expression as a mechanism of nutritional programming and developmental origins of health and disease

基因表达的表观遗传调控作为营养规划和健康与疾病发育起源的机制

• 批准号: BB/D01235X/1
• 负责人: Miguel Constancia
• 金额: $ 33.8万
• 依托单位: Babraham Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD01235X%2F1
• 关键词: Epigenetic; regulation; gene; expression; mechanism

The diet of an individual has important health issues at any stage of life - 'we are what we eat' after all. However, there is evidence to suggest that the diet of a pregnant woman is particularly important as it has major long-term implications on the health of her offspring - so, in some ways 'we also are what our mothers ate during pregnancy'. Normal term babies born from mothers with poor nutrition during pregnancy usually have a low weight. It has been shown that individuals with a low birth weight are not only less likely to survive delivery but are also at substantially increased risk of developing various common diseases such as diabetes, hypertension and heart disease in adulthood. The underlying causes of the relationship between poor early growth and disease in adulthood are not known, but we believe that the quality of the diet of women during pregnancy is critically important. Many of our attempts to decipher mechanisms of human diseases both rely and benefit from studying animal models. We have shown in a rodent model that if pregnant animals have too little protein during pregnancy their babies are small at birth and develop diabetes in adulthood. We have identified important genes in the pancreas that are expressed at low levels in the offspring of protein-restricted mothers compared to control animals. We now plan further to study these animals to understand how a restricted diet is able to perturb expression of key genes involved in pathogenesis of diabetes. We are particularly interested in studying epigenetic mechanisms - that is mechanisms able to change activity of a gene without altering its DNA sequence - that could be triggered by nutritional changes during pregnancy. We also want to know more precisely at which time/s during pregnancy the quality of the mother's diet is most important for giving birth to healthy babies. This will enable us to both identify at risk individuals and to develop intervention strategies to improve the health of both the pregnant women and their offspring.

一个人的饮食在生命的任何阶段都有重要的健康问题-毕竟“我们吃什么就是什么”。然而，有证据表明，孕妇的饮食特别重要，因为它对她的后代的健康有重大的长期影响-所以，在某些方面，“我们也是我们母亲在怀孕期间吃的东西”。怀孕期间营养不良的母亲所生的正常足月婴儿通常体重较低。已经表明，出生体重低的人不仅不太可能在分娩后存活，而且在成年后患糖尿病、高血压和心脏病等各种常见疾病的风险也大大增加。早期生长不良与成年期疾病之间关系的根本原因尚不清楚，但我们相信怀孕期间女性的饮食质量至关重要。我们对人类疾病机制的许多解读都依赖于动物模型的研究，并从中受益。我们已经在啮齿动物模型中表明，如果怀孕动物在怀孕期间蛋白质摄入过少，它们的婴儿出生时很小，成年后会患上糖尿病。我们已经确定了胰腺中的重要基因，与对照动物相比，这些基因在蛋白质限制的母亲的后代中表达水平较低。我们现在计划进一步研究这些动物，以了解限制饮食如何能够干扰参与糖尿病发病机制的关键基因的表达。我们特别感兴趣的是研究表观遗传机制-即能够改变基因活性而不改变其DNA序列的机制-这可能是由怀孕期间的营养变化引发的。我们还想更准确地了解在怀孕期间的哪些时间，母亲的饮食质量对生下健康的婴儿最重要。这将使我们能够识别高危人群，并制定干预策略，以改善孕妇及其后代的健康。

项目成果

Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets.

• DOI: 10.1007/s00125-015-3837-8
• 发表时间: 2016-03
• 期刊: Diabetologia
• 影响因子: 8.2
• 作者: Sandovici I;Hammerle CM;Cooper WN;Smith NH;Tarry-Adkins JL;Dunmore BJ;Bauer J;Andrews SR;Yeo GS;Ozanne SE;Constância M
• 通讯作者: Constância M

Intergenerational epigenetic inheritance in models of developmental programming of adult disease.

• DOI: 10.1016/j.semcdb.2015.06.006
• 发表时间: 2015-07
• 期刊: Seminars in cell & developmental biology
• 影响因子: 7.3
• 作者: Fernandez-Twinn DS;Constância M;Ozanne SE
• 通讯作者: Ozanne SE

Maternal diet, aging and diabetes meet at a chromatin loop.

• DOI: 10.18632/aging.100330
• 发表时间: 2011-05
• 期刊: Aging
• 作者: Ozanne SE;Sandovici I;Constância M
• 通讯作者: Constância M