Mechanisms by which early-life nutritional factors program postnatal metabolism

生命早期营养因素影响产后代谢的机制

• 批准号: RGPIN-2016-03773
• 负责人: Reimer, Raylene
• 金额: $ 4.44万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631565
• 关键词: Mechanisms; early; life; nutritional; factors

Environmental exposures during critical periods of development can have permanent effects on tissue structure and metabolism. Of the environmental factors known to have such effects, maternal nutrition is one of the most well-studied. More recently, fathers' diet or paternal nutrition has been shown to also play a role in metabolic programming of offspring. We have shown that maternal diets high in protein impair glucose metabolism in offspring while diets high in prebiotic fiber reduce adiposity and improve glucose homeostasis. Despite an abundance of evidence for the ‘programming’ of offspring metabolism, our understanding of the mechanisms by which early life events cause changes in tissue structure and function later in life is incomplete. Epigenetic processes have emerged as a plausible mechanism and include alterations in DNA methylation, modification of histone tails and expression of non-coding RNAs such as microRNAs. Furthermore, one of the links between maternal nutrition and offspring metabolism may be found in maternal milk oligosaccharides, which act as fermentable substrate in the infant gut and thereby modulate gut microbiota and the metabolites they produce. Whether or not changes in these milk oligosaccharides provides a mechanistic explanation of how maternal milk programs offspring metabolism is not known.

发育关键时期的环境暴露会对组织结构和新陈代谢产生永久性影响。在已知具有此类影响的环境因素中，孕产妇营养是研究最深入的因素之一。最近，父亲的饮食或父亲的营养已被证明在后代的代谢规划中也发挥着作用。我们已经证明，富含蛋白质的母体饮食会损害后代的葡萄糖代谢，而富含益生元纤维的饮食可以减少肥胖并改善葡萄糖稳态。尽管有大量证据表明后代新陈代谢的“编程”，但我们对早期生命事件导致晚年组织结构和功能变化的机制的理解并不完整。表观遗传过程已成为一种合理的机制，包括 DNA 甲基化的改变、组蛋白尾部的修饰以及非编码 RNA（如 microRNA）的表达。此外，母体营养和后代代谢之间的联系之一可能存在于母乳寡糖中，母乳寡糖充当婴儿肠道中的可发酵底物，从而调节肠道微生物群及其产生的代谢物。这些乳汁寡糖的变化是否为母乳如何影响后代新陈代谢提供了机制解释尚不清楚。