Preclinical research suggested that maternal exercise is a viable strategy for reducing the transmission of intergenerational metabolic dysfunction induced by maternal obesity. The advantages of maternal activity on offspring health may result from a variety of reasons, including DNA demethylation of important hepatic genes, which leads to improved glucose metabolism in offspring. Histone modification is another epigenetic regulator, although the effects of maternal obesity and exercise on histone methylation in kids are unknown.

Researchers discovered that a high-fat diet (HFD; 60% kcal from fat) during pregnancy caused dysregulation of offspring liver glucose metabolism in C57BL/6 via a mechanism involving increased reactive oxygen species, WD repeat-containing 82 (WDR82) carbonylation, and inactivation of histone H3 lysine 4 (H3K4) methyltransferase, resulting in decreased H3K4me3 at the promoters of glucose metabolic genes. 

Surprisingly, if the HFD-fed dams were exercised during pregnancy, the full signal was restored. In hepatoblasts, WDR82 overexpression replicated the effects of maternal exercise on H3K4me3 levels. Placental superoxide dismutase 3 (SOD3), but not N-acetylcysteine antioxidant therapy, was required for the control of H3K4me3, gene expression, and glucose metabolism. Maternal activity controls a multicomponent epigenetic mechanism in the fetal liver, which results in the transfer of exercise advantages to children.