Abstract
Recently, Developmental Origins of Health and Disease (DOHaD) theory, in which nutritional environment in gestation and lactation periods may determine the life-style diseases such as obesity and type 2 diabetes has been proposed. Modification of gene expression via epigenetics, particularly DNA methylation, is a candidate of the molecular mechanism of the DOHaD theory. We have demonstrated that fatty acid β-oxidation genes including fibroblast growth factor 21 gene (Fgf21) are subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the mouse liver during the postnatal period. We have also revealed that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood, which may partly determine diet-induced obesity in adulthood. Thus, the DNA methylation status of Fgf21 as an epigenetic memory may be a molecular entity of the DOHaD theory regarding obesity. On the other hand, it has been revealed that vitamin C plays an important role in PPARα -independent DNA demethylation in the mouse liver during the postnatal period.
