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

Author

Listed:
  • Xunmei Yuan

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Kazutaka Tsujimoto

    (Tokyo Medical and Dental University)

  • Koshi Hashimoto

    (Tokyo Medical and Dental University)

  • Kenichi Kawahori

    (Tokyo Medical and Dental University)

  • Nozomi Hanzawa

    (Tokyo Medical and Dental University)

  • Miho Hamaguchi

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Takami Seki

    (Tokyo Medical and Dental University)

  • Makiko Nawa

    (Tokyo Medical and Dental University)

  • Tatsuya Ehara

    (Tokyo Medical and Dental University
    Wellness and Nutrition Science Institute, Morinaga Milk Industry Co., Ltd)

  • Yohei Kitamura

    (Wellness and Nutrition Science Institute, Morinaga Milk Industry Co., Ltd)

  • Izuho Hatada

    (Gunma University)

  • Morichika Konishi

    (Kobe Pharmaceutical University)

  • Nobuyuki Itoh

    (Kyoto University Graduate School of Medicine)

  • Yoshimi Nakagawa

    (University of Tsukuba
    University of Tsukuba)

  • Hitoshi Shimano

    (University of Tsukuba
    University of Tsukuba)

  • Takako Takai-Igarashi

    (Tohoku Medical Megabank Organization)

  • Yasutomi Kamei

    (Kyoto Prefectural University)

  • Yoshihiro Ogawa

    (Tokyo Medical and Dental University
    Kyushu University
    Japan Agency for Medical Research and Development, CREST
    Tokyo Medical and Dental University)

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.

Suggested Citation

  • Xunmei Yuan & Kazutaka Tsujimoto & Koshi Hashimoto & Kenichi Kawahori & Nozomi Hanzawa & Miho Hamaguchi & Takami Seki & Makiko Nawa & Tatsuya Ehara & Yohei Kitamura & Izuho Hatada & Morichika Konishi , 2018. "Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03038-w
    DOI: 10.1038/s41467-018-03038-w
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