Early Life Nutrition Research Unit, Academic Division of Child Health, and Nottingham Respiratory Medicine Biomedical Research Unit, School of Clinical Sciences, University Hospital Nottingham, Nottingham, United Kingdom.
Am J Clin Nutr. 2011 Dec;94(6 Suppl):1953S-1958S. doi: 10.3945/ajcn.110.001040. Epub 2011 May 4.
Adult health is dependent, in part, on maternal nutrition and growth during early life, which may independently affect insulin sensitivity, body composition, and overall energy homeostasis. Since the publication of the "thrifty phenotype hypothesis" by Hales and Barker (Diabetologia 1992;35:595-601), animal experiments have focused on establishing the mechanisms involved, which include changes in fetal cortisol, insulin, and leptin secretion or sensitivity. Intrauterine growth retardation can be induced by either prolonged modest changes in maternal diet or by more severe changes in uterine blood supply near to term. These contrasting challenges result in different amounts of cellular stress in the offspring. In addition, shifts in the transcriptional activity of DNA may produce sustained metabolic adaptations. Within tissues and organs that control metabolic homeostasis (eg, hypothalamus, adipose tissue, stomach, skeletal muscle, and heart), a range of phenotypes can be induced by sustained changes in maternal diet via modulation of genes that control DNA methylation and by histone acetylation, which suggests epigenetic programming. We now need to understand how changes in maternal diet affect DNA and how they are conserved on exposure to oxidative stress. A main challenge will be to establish how the dietary environment interacts with the programmed phenotype to trigger the development of metabolic disease. This may aid in the establishment of nutrigenomic strategies to prevent the metabolic syndrome.
成人健康部分依赖于母体在生命早期的营养和生长状况，这可能会独立影响胰岛素敏感性、身体成分和整体能量稳态。自 Hales 和 Barker 发表“节俭表型假说”（1992 年《糖尿病学》第 35 卷：595-601）以来，动物实验一直专注于确定相关机制，其中包括胎儿皮质醇、胰岛素和瘦素分泌或敏感性的变化。宫内生长迟缓可以通过延长母体饮食的适度变化或接近足月时子宫血液供应的更严重变化来诱发。这些截然不同的挑战导致后代细胞应激的程度不同。此外，DNA 转录活性的转变可能会产生持续的代谢适应。在控制代谢稳态的组织和器官（例如，下丘脑、脂肪组织、胃、骨骼肌和心脏）中，通过调节控制 DNA 甲基化的基因和组蛋白乙酰化，可以诱导一系列表型发生持续变化，这表明存在表观遗传编程。我们现在需要了解母体饮食的变化如何影响 DNA，以及它们在暴露于氧化应激时如何被保存。主要挑战将是确定饮食环境如何与编程表型相互作用，从而引发代谢疾病的发展。这可能有助于建立营养基因组策略来预防代谢综合征。
