Nutrition and early life programming: exploring epigenetic mechanisms

生命早期的营养压力会对健康产生长期影响。产后早期生命的快速增长与晚年肥胖、心血管疾病和2型糖尿病等常见疾病的发病率增加有关。产后早期营养不良与后期健康不良之间的联系机制尚未得到很好的界定。早产儿被鼓励体重迅速增加，但这对成人健康有重要影响。通过研究早产儿，现在10-12岁，他们参加了一项产后营养试验，我们不仅可以收集到不同婴儿喂养方案对健康的影响的重要信息，还可以收集到相关的分子机制。该项目旨在研究允许在细胞水平上“记忆”早期营养的分子机制。基因组在营养暴露的情况下被“标记”，这些标记可以诱导基因开启和关闭的稳定变化。表观遗传学是指用这些化学标记修饰基因组，是后基因组科学的一个新兴领域。新技术将用于研究120名早产儿的表观遗传标记和基因表达。这些孩子参加了一项营养试验，从怀孕36周到6个月大，他们被喂食三种不同的饮食之一。它们的成长和发展已经持续了10-12年。观察到的表观遗传状态和基因表达的变化将与儿童健康的差异有关，例如身体成分、血压、葡萄糖和胰岛素水平以及参与脂肪代谢的激素水平。该项目将使用生物技术和生物信息学方面的新工具来研究营养如何影响基因组，以及这可能如何对健康产生长期持久的影响。

Nutritional stresses in early life have long-lasting effects on health. Rapid growth in early postnatal life has been linked to increased incidence of common diseases such as obesity, cardiovascular disease and type 2 diabetes in later life. The mechanisms that link early post-natal nutrition with later ill health have not been well defined. Infants born preterm are encouraged to gain weight rapidly but this has important implications for adult health. By studying children who were born preterm, now aged 10-12 years, who participated in a post-natal nutritional trial we can glean important information not only about the health consequences of different infant feeding regimen, but also about the molecular mechanisms involved. This project aims to examine the molecular mechanisms that allow early nutrition to be 'memorised' at a cellular level. The genome is 'marked' in response to nutritional exposures and these markings can induce stable changes in which genes are switched on and switched off. Epigenetics refers to the decoration of the genome by these chemical markings and is an emerging field of post-genomic science. New technologies will be used to study epigenetic markings and gene expression in 120 children born preterm. These children took part in a nutritional trial and were fed one of three different diets from 36 weeks gestation to 6 months of age. Their growth and development has been followed over the last 10-12 years. Changes observed in epigenetic status and in gene expression will be related to differences in the health of the children, such as body composition, blood pressure, glucose and insulin levels and levels of hormones involved in fat metabolism. This project will use new tools in biotechnology and bioinformatics to study how nutrition influences the genome and how this may have long lasting effects on health.