Developmental Epigenomics and Metabolic Disease

Abstract

Organisms have evolved the processes of developmental plasticity to adjust their developmental trajectory in response to early life exposure to environ- mental cues. The potentially adaptive nature of such anticipatory responses is aimed at promoting Darwinian fitness; however, a mismatch between the induced phenotype and the later life environment increases the risk of disease, as evolution- ary processes act to maximize reproductive success and not to maintain health and longevity. We focus on the developmental origins of later life metabolic disease in humans particularly with respect to early life under- and overnutrition and review the experimental, epidemiological, and clinical evidence implicating epigenetic mechanisms in the modulation of disease risk. There is growing evidence that epigenetic marks—and hence possibly disease risk—may be transgenerationally transmitted via non-genomic pathways of inheritance. This has implications both for the perpetuation of disease risk across generations and for the potential impact on evolution should epigenetic marks become genomically fixed. We also discuss the potential of developmental epigenomics in identifying prognostic biomarkers and therapeutic targets and raise several technical and methodological caveats to be borne in mind when undertaking and interpreting epigenomic research.