Mechanisms by which early-life nutritional factors program postnatal metabolism

发育关键时期的环境暴露会对组织结构和代谢产生永久性影响。在已知有这种影响的环境因素中，母亲的营养是研究得最充分的因素之一。最近，父亲的饮食或父亲的营养也被证明在后代的代谢程序中起作用。我们已经证明，高蛋白质的母亲饮食会损害后代的葡萄糖代谢，而高益生元纤维的饮食会减少肥胖并改善葡萄糖稳态。尽管有大量证据表明后代代谢的“编程”，但我们对早期生活事件导致生命后期组织结构和功能变化的机制的理解是不完整的。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，组蛋白尾部的修饰和非编码rna（如microRNAs）的表达。此外，母体营养与后代代谢之间的联系之一可能存在于母乳低聚糖中，低聚糖在婴儿肠道中充当可发酵底物，从而调节肠道微生物群及其产生的代谢物。这些牛奶低聚糖的变化是否提供了母乳如何控制后代代谢的机制解释尚不清楚。

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.