Early environmental factors, alteration of epigenetic marks and metabolic disease susceptibility.

The environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Early-life nutrition and stress are among the best documented examples of such conditions because they influence the adult risk of developing metabolic diseases, such as type 2 diabetes mellitus (T2D) and cardiovascular diseases. It is now becoming increasingly accepted that environmental compounds including nutrients can produce changes in the genome activity that in spite of not altering DNA sequence can produce important, stable and transgenerational alterations in the phenotype. Epigenetic changes, in particular DNA methylation and histone acetylation/methylation, provide a 'memory' of developmental plastic responses to early environment and are central to the generation of phenotypes and their stability throughout the life course. Their effects may only become manifest later in life, e.g. in terms of altered responses to environmental challenges.