Maternal fructose-induced oxidative stress occurs and epigenetic regulation in offspring hippocampi.

Fructose consumption is rising globally, but maternal high fructose intake might adversely affect offspring. Our previous report demonstrated that excess maternal fructose intake impairs hippocampal function in offspring, indicating that the hippocampi of offspring are highly sensitive to maternal fructose. Here, we examined the effect of maternal high fructose on mitochondrial physiology and uncoupling protein (UCP) expression. Rat dams received a 20% fructose solution during gestation and lactation. Immediately after weaning, offspring hippocampi were isolated. Maternal high fructose consumption attenuated the mitochondrial O consumption rate and stimulated lipid hydroperoxide production in the hippocampi of offspring. Reduced and mitochondrial transcription factor A () mRNA levels were also observed after maternal exposure to fructose. We assessed the promoter regions of both genes and found that this treatment enhanced DNA methylation levels. In addition, luciferase assays showed that this DNA methylation could reduce the transcription of both genes. Chromatin immunoprecipitation analysis demonstrated that specificity protein 1 binding to the promoter regions was reduced by DNA methylation. In addition, knockdown induced the up-regulation of reactive oxygen species levels in a rat brain glioma cell line, whereas reduced O consumption was observed with knockdown. Maternal high fructose intake thus induces reduced O oxygen consumption and increases oxidative stress in offspring, at least partly through epigenetic mechanisms involving and .-Yamada, H., Munetsuna, E., Yamazaki, M., Mizuno, G., Sadamoto, N., Ando, Y., Fujii, R., Shiogama, K., Ishikawa, H., Suzuki, K., Shimono, Y., Ohashi, K., Hashimoto, S. Maternal fructose-induced oxidative stress occurs and epigenetic regulation in offspring hippocampi.