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.***The overall objective of this program is to identify mechanisms by which early prenatal and postnatal nutrition program glucose and lipid metabolism in offspring. The overarching hypothesis is that early exposure to diets high in protein or prebiotic fiber program offspring metabolism via epigenetic mechanisms. Milk oligosaccharides, shown by us to be altered with maternal diet, may be one maternal factor that influences metabolic response in offspring.***Our scientific approach will capitalize on our well-established NSERC-funded rat model of developmental programming. We will examine the epigenetic mechanisms, chiefly miRNA expression, by which maternal diets high in protein or fiber program offspring metabolism. Similarly, we will feed male breeder rats diets high in protein or fiber and examine the biochemical, genetic and epigenetic mechanisms by which fathers' dietary intake affects the offspring. We previously demonstrated that a maternal high prebiotic fiber diet increased certain oligosaccharides in maternal milk. Using artificial rearing and rat milk replacer supplemented with milk oligosaccharides, we will examine the mechanisms by which oligosaccharides affect gut microbiota, intestinal development and glucose and lipid metabolism in young rats.***The goal of this work is to expand our understanding of the mechanisms by which early nutritional influences (maternal, paternal, postnatal) affect long-term metabolism in offspring. The effects of common (protein and fiber) and novel (milk oligosaccharides) food ingredients will be examined.**