ABSTRACT
The various non-Mendelian features of obesity, such as the high degree of discordance between monozygote (MZ) twins, clinical differences between men and women, and fluctuations in the course of the disease, are consistent with epigenetic mechanisms for the influence of fetal environment on adult phenotype (1). Thus, in addition to harboring a number of gene variants conferring susceptibility (2), individuals with metabolic syndrome, obesity, and type 2 diabetes (T2D) may show a lifelong imbalance between energy intake and energy expenditure as well as incorrect “EpiG programming” during their early development as a result of placental insufficiency, inadequate maternal body composition, nutritional imbalance, and metabolic disturbances during critical time windows of development (3,4), which may have a persistent effect on the health of the offspring and may even be transmitted to the next generation. The environment modifies the epigenetic patterns of susceptible genes during development in such a way that key functions, such as appetite control, metabolic balance, and fuel utilization are permanently modified. Moreover, epigenetic alterations occur day after day and accumulate over time, as age-, diet-, and disease-related deteriorations interact with several other processes. The transgenerational effects (TGEs) of incorrectly erased epigenetic marks resulting from the behavior and nutrition of previous generations may complete the picture. Lifetimes shape the multitude of epigenomes not only within but also across generations (5).
