Towards the mechanism of early-life programming: Consequences of a maternal western diet

Maternal diet is associated with the development of metabolism-related and other diseases in the offspring. Underlying mechanisms and molecular markers are only starting to be revealed. In this research project, we explored the physiological and molecular impact of maternal western-style diet on the development of the offspring. Mice were exposed to either a low fat/low cholesterol diet (LFD) or a western-style high fat/high cholesterol diet (WSD) before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at different developmental stages. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. Exclusively male offspring had significantly higher body weight and a non-alcoholic fatty liver-phenotype upon maternal WSD. We conclude that maternal WSD affects physiological parameters and induces vital changes in the molecular profile of the liver in offspring. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity, which in part might be related to a differential development of the placenta. We describe that the labyrinth diameter is larger in male placentas compared to the female placentas, which let us speculate that the male placenta supports transport of excess maternal nutrients to the male fetus. In addition we studied DNA methylation changes that might facilitate programming effects to persist into adulthood. In our mice we found a core set of specific methylation patterns corresponding to human steatohepatitis.