Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter

FASEB J. 2018 May;32(5):2549-2562. doi: 10.1096/fj.201700783RR. Epub 2018 Jan 8.


Recent increases in fructose consumption have raised concerns about the potential adverse intergenerational effects of excess fructose intake. In the present study, we investigated whether excess maternal fructose intake affects hippocampal function in offspring. Female Sprague-Dawley rats were divided into 3 experimental groups: one group received distilled water, one group received 20% fructose water, and one group received 20% glucose water in addition to standard chow during gestation and lactation. Hippocampal function of offspring was evaluated by using novel object recognition and fear conditioning tests. Impaired cognitive performance was observed in the offspring of fructose-fed dams at postnatal d 60, potentially a result of decreased hippocampal neurogenesis. Real-time PCR analysis demonstrated that offspring from fructose-fed dams exhibited decreased brain-derived neurotrophic factor ( BDNF) gene expression, whereas pyrosequencing assays revealed increased DNA methylation at the BDNF promoter. The potential association between BDNF transcription and levels of DNA methylation was confirmed on the basis of luciferase activity. Furthermore, longitudinal analysis revealed that increased methylation of the BDNF promoter region was maintained at least until rats reached maturity. These results indicate that epigenetic changes associated with BDNF may underlie hippocampal dysfunction that is induced by early-life exposure to excess maternal fructose consumption.-Yamazaki, M., Yamada, H., Munetsuna, E., Ishikawa, H., Mizuno, G., Mukuda, T., Mouri, A., Nabeshima, T., Saito, K., Suzuki, K., Hashimoto, S., Ohashi, K. Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter.

Keywords: DOHaD; cognitive function; early-life adversity; maternal nutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • DNA Methylation / drug effects
  • Epigenesis, Genetic / drug effects*
  • Female
  • Fructose / adverse effects*
  • Fructose / pharmacology
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Maternal Exposure / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Prenatal Exposure Delayed Effects / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Fructose