Developmental programming and transgenerational transmission of obesity

Abstract

Obesity is an increasing global health concern that is commonly attributed to dietary and lifestyle changes, particularly intake of high calorie diets and reduced physical activity. Obesity and its related cardiometabolic disorders are also major issues in developing societies transitioning toWestern-style diets and lifestyles. It is well established that alterations in the early life period and impacts upon sensitive periods of developmental plasticity can lead to a range of adverse phenotypic outcomes and predispose to later obesity. Human cohorts and experimental animal models have reported clear linkages between the early life environment, particularly the maternal nutritional milieu, and increased risk for offspring to develop offspring and related cardiometabolic disorders. Increasing evidence is also building around the paternal contribution to such programming effects, including paternal obesity. This process, via both the maternal and paternal lineage, is preferentially called "developmental programming" and sits under the Developmental Origins of Health and Disease (DOHaD) framework. Moreover, developmental programming is now regarded as a transgenerational phenomenon with a number of studies showing metabolic disorders passing to future generations, even in the absence of further environmental insults. Such disease transmission is commonly seen as a mode of "epigenetic inheritance" with both somatic and germline inheritance of altered epigenetic marks resulting in altered phenotypes that may persist across generations. In addition, there are data suggesting nongenomic components to transgenerational programming of obesity including direct effects on the developing fetus via a suboptimal intrauterine environment and maternal constraint. An increased understanding of how developmental programming effects are transmitted is essential to allow initiatives to be implemented to break the current cycle of obesity across generations.