Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver

Kenichi Kawahori, Yoshitaka Kondo, Xunmei Yuan, Yuki Kawasaki, Nozomi Hanzawa, Kazutaka Tsujimoto, Fumiko Wada, Takashi Kohda, Akihito Ishigami, Tetsuya Yamada, Yoshihiro Ogawa, Koshi Hashimoto

Research output: Contribution to journalArticlepeer-review

Abstract

Ascorbic acid (AA, vitamin C) serves as a cofactor for ten-eleven translocation (TET) enzymes and induces DNA demethylation in vitro. However, its role in DNA demethylation in vivo remains unclear. We previously reported that DNA demethylation in the mouse liver was enhanced during the suckling period. Therefore, we hypothesized that DNA demethylation is enhanced in an AA-dependent manner during the suckling period. To examine our hypothesis, we employed wild-type (WT) mice, which synthesize AA, and senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA, and analyzed the DNA methylation status in the livers of offspring in both the suckling period and adulthood. SMP30/GNL KO offspring showed DNA hypermethylation in the liver possibly due to low plasma and hepatic AA levels during the suckling period despite the administration of rescue-dose AA to dams. Furthermore, DNA hypermethylation of the fibroblast growth factor 21 gene (Fgf21), a PPARα target gene, persisted into adulthood. In contrast, a high-dose AA administration to SMP30/GNL KO dams during the lactation period restored DNA demethylation in the livers of offspring. Even though a slight increase was observed in plasma AA levels with the administration of rescue-dose AA to WT dams during the gestation and lactation periods, DNA demethylation in the livers of offspring was minimally enhanced. The present results demonstrate that AA intake during the suckling period is required for proper DNA demethylation in the liver.

Original languageEnglish
Article number21228
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - 2020 Dec

ASJC Scopus subject areas

  • General

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