Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

Xunmei Yuan, Kazutaka Tsujimoto, Koshi Hashimoto, Kenichi Kawahori, Nozomi Hanzawa, Miho Hamaguchi, Takami Seki, Makiko Nawa, Tatsuya Ehara, Yohei Kitamura, Izuho Hatada, Morichika Konishi, Nobuyuki Itoh, Yoshimi Nakagawa, Hitoshi Shimano, Takako Takai-Igarashi, Yasutomi Kamei, Yoshihiro Ogawa

Research output: Contribution to journalArticle

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Abstract

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.

Original languageEnglish
Article number636
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

obesity
diets
methylation
fibroblasts
Nutrition
liver
Epigenomics
genes
Liver
mice
Obesity
Genes
Peroxisome Proliferator-Activated Receptors
Modulation
Diet
modulation
deoxyribonucleic acid
Methylation
DNA Methylation
activation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood. / Yuan, Xunmei; Tsujimoto, Kazutaka; Hashimoto, Koshi; Kawahori, Kenichi; Hanzawa, Nozomi; Hamaguchi, Miho; Seki, Takami; Nawa, Makiko; Ehara, Tatsuya; Kitamura, Yohei; Hatada, Izuho; Konishi, Morichika; Itoh, Nobuyuki; Nakagawa, Yoshimi; Shimano, Hitoshi; Takai-Igarashi, Takako; Kamei, Yasutomi; Ogawa, Yoshihiro.

In: Nature communications, Vol. 9, No. 1, 636, 01.12.2018.

Research output: Contribution to journalArticle

Yuan, X, Tsujimoto, K, Hashimoto, K, Kawahori, K, Hanzawa, N, Hamaguchi, M, Seki, T, Nawa, M, Ehara, T, Kitamura, Y, Hatada, I, Konishi, M, Itoh, N, Nakagawa, Y, Shimano, H, Takai-Igarashi, T, Kamei, Y & Ogawa, Y 2018, 'Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood', Nature communications, vol. 9, no. 1, 636. https://doi.org/10.1038/s41467-018-03038-w
Yuan, Xunmei ; Tsujimoto, Kazutaka ; Hashimoto, Koshi ; Kawahori, Kenichi ; Hanzawa, Nozomi ; Hamaguchi, Miho ; Seki, Takami ; Nawa, Makiko ; Ehara, Tatsuya ; Kitamura, Yohei ; Hatada, Izuho ; Konishi, Morichika ; Itoh, Nobuyuki ; Nakagawa, Yoshimi ; Shimano, Hitoshi ; Takai-Igarashi, Takako ; Kamei, Yasutomi ; Ogawa, Yoshihiro. / Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood. In: Nature communications. 2018 ; Vol. 9, No. 1.
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