Exploring possible epigenetic mediation of early-life environmental exposures on adiposity and obesity development.

Abstract

Within populations, individual adiposity tends to remain at the same level relative to other individuals from birth through adulthood, leading to the so-called tracking phenomenon.1–3 However, following individuals over time with multiple repeated measures of the phenotype can reveal fluctuations, with some departing permanently from their initial trajectory.4 A better understanding of tracking and of departure from it may help in finding the optimal conditions for preventing the development of a health-challenging state of obesity. Longitudinal tracking in body composition is likely to be attributable to a set of determinants exhibiting stability through time, and departures from this would be the result of temporally unstable events.5 Long-lasting effects after short-term environmental insults have been identified in response to transient exposure during the ‘critical’ periods of gestation and early infancy,6 sometimes with a much longer time interval between exposure and effect than is required for changes in body composition. This suggests that alternative systems of phenotypic ‘lag’ and ‘memory’ may exist which have marked effects on an individual’s trajectory. Given that the biological mechanisms of the long-term effects of early time-limited exposures are largely unknown, the challenge is to identify biological changes induced by early exposures that are stable over long periods of time, possibly throughout the life course, which may influence later adiposity development. One plausible contribution to different patterns of time-dependent phenotypic variation is that epigenetic signatures of the exposure may act (in differing ways) as a memory of early-life insult in the genome.7,8 Here we present examples of epidemiological observations suggesting the existence of the long-term effects of short-term early exposures influencing adiposity and risk of obesity development. We review the current biological evidence for epigenetic alterations associated with the early-life exposures and with the adiposity phenotype. We suggest that these persisting, sometimes lagged, effects are mediated by long-term epigenetic modifications induced by the earlier exposures, and we outline types of studies that may be used to unravel the effects. Finally, we discuss the utility of knowing whether epigenetic changes are mediating the early exposures, in order to improve the prevention and treatment of obesity.