Mechanisms by which early-life nutritional factors program postnatal metabolism

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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.