Developmental Programming and Transgenerational Transmission of Obesity

The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero environment in the perpetuation of programmed phenotypes. A better understanding of how developmental programming effects are transmitted is essential for the implementation of initiatives aimed at curbing the current obesity crisis.