Abstract:
The phenomenon whereby an individual’s early life experiences modulate subsequent susceptibility to disease risk is known as the “developmental origins of health and disease” (DOHaD). This chapter focuses on obesity and associated metabolic disease, reviewing this research domain through the lens of an evolutionary developmental biology (evo-devo) conceptual framework. At the molecular level, we use early life nutrition as an illustrative example to review the rapidly accumulating experimental, clinical and epidemiological evidence that epigenetic mechanisms are a key component underlying developmental pathways affecting the risk of obesity and related diseases. Early overnutrition involving evolutionarily novel circumstances such as maternal obesity and gestational diabetes, while potentially representing a non-adaptive pathway to DOHaD, may also be underpinned by epigenetic mechanisms. The evidence that epigenetic dysregulation underlies the pathology of obesity and type 2 diabetes in adults is reviewed, as is the therapeutic potential of developmental epigenomics in improving human health.