Regulation of protein synthesis as a mechanism of nutritional programming and developmental origins of optimal health

蛋白质合成的调节作为营养规划和最佳健康发育起源的机制

• 批准号: BB/F014279/2
• 负责人: Anne Willis
• 金额: $ 13.99万
• 依托单位: MRC Toxicology Unit
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF014279%2F2
• 关键词: Regulation; protein; synthesis; mechanism; nutritional

The diet of an individual can have important health consequences at any stage of life. However there is evidence to suggest that the diet of women during pregnancy and while breastfeeding is particularly important as it has major long-term implications for the health of her baby. 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 type 2 diabetes, high blood pressure and heart disease in adulthood and are more likely to die at a younger age. The underlying causes of the relationship between early growth and adult disease are not known, but it is thought that the quality of the diet of women during pregnancy and breastfeeding is critically important. Studies in animal models can be very useful in helping to decipher mechanisms of human diseases. We have shown that if pregnant and lactating rats have too little protein in their diet their offspring are small at birth and later develop diabetes. We have studied fat tissue and have identified key proteins that are much less abundant both in young men who had a low birth weight and in offspring of protein restricted rat mothers. The central dogma of biology is that the genetic material DNA is copied to an intermediary molecule RNA that is then translated into proteins. Our recent results suggest that the second step of this process is permanently altered (or 'programmed') in the offspring of animals or humans that had a sub-optimal diet. In our project we will study RNA from rat and human fat cells to identify new genes that are programmed to be expressed at different levels as a result of poor early life nutrition. We will also determine why it is that their RNA is not translated properly to make the corresponding proteins. Understanding these processes will enable us to identify individuals at risk and to develop intervention strategies to improve the health of pregnant and breast-feeding women and their offspring.

一个人的饮食在生命的任何阶段都可能对健康产生重要影响。然而，有证据表明，妇女在怀孕期间和哺乳期间的饮食特别重要，因为它对婴儿的健康有重大的长期影响。研究表明，出生体重低的人不仅不太可能在分娩后存活下来，而且在成年后患2型糖尿病、高血压和心脏病的风险也大大增加，更有可能在年轻时死亡。早期生长和成人疾病之间关系的根本原因尚不清楚，但人们认为，妇女在怀孕和哺乳期间的饮食质量至关重要。动物模型的研究在帮助解释人类疾病的机制方面非常有用。我们已经证明，如果怀孕和哺乳期大鼠的饮食中蛋白质太少，它们的后代出生时很小，后来会患上糖尿病。我们已经研究了脂肪组织，并确定了关键蛋白质，这些蛋白质在出生体重低的年轻男性和蛋白质限制的大鼠母亲的后代中含量要少得多。生物学的中心法则是，遗传物质DNA被复制到中间分子RNA，然后RNA被翻译成蛋白质。我们最近的研究结果表明，这个过程的第二步在饮食不理想的动物或人类的后代中被永久改变（或“编程”）。在我们的项目中，我们将研究来自大鼠和人类脂肪细胞的RNA，以识别由于早期营养不良而在不同水平上表达的新基因。我们还将确定为什么它们的RNA没有被正确翻译成相应的蛋白质。了解这些过程将使我们能够识别处于风险中的个人，并制定干预战略，以改善孕妇和哺乳期妇女及其后代的健康。

项目成果

Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.

• DOI: 10.1038/cdd.2013.135
• 发表时间: 2014-01
• 期刊: Cell death and differentiation
• 影响因子: 12.4

Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes.

2 型糖尿病中母亲饮食对脂肪组织 miR-483-3p 和 GDF-3 表达的编程。

• DOI: 10.17863/cam.10501
• 发表时间: 2012
• 作者: Ferland-McCollough D