I'm eating for two: parental dietary effects on offspring metabolism

Abstract

It has long been understood that the pathogenesis of complex diseases such as diabetes includes both genetic and environmental components. More recently, it has become clear that not only does an individual's environment influence their own metabolism, but in some cases, the environment experienced by their parents may also contribute to their risk of metabolic disease. Here, we review the evidence that parental diet influences metabolic phenotype in offspring in mammals and provide a current survey of our mechanistic understanding of these effects.

Figure 1. Schematic for maternal effect paradigms

Maternal effect paradigms typically involve altered access to nutrients, with key paradigms including under or overnutrition prior to conception, during preimplantation development, or later in pregnancy. Phenotypes are then typically studied in F1 offspring. In a subset of experimental systems, F1 offspring are bred either with control animals or with one another to identify multigenerational effects of fetal undernutrition.

Figures 2/3. Mechanisms linking fetal nutrient supply to later phenotypes

Uteroplacental insufficiency decreases availability of key substrates such as oxygen and glucose to the fetus. Altered substrate availability (e.g. decreased acetyl Co-A, or S-Adenosyl methionine) can directly influence epigenetic mediators resulting in epigenetic modifcations of key genes. Decreased levels of glucose and oxygen can also impair mitochondrial function and increase production of ROS. These processes can have a detrimental affect on numerous cellular pathways culminating in fetal programming.