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

doi:10.1038/s41467-018-03038-w

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

^*Corresponding author for this work

Complex Biosystem Research, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

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 language	English
Article number	636
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03038-w
State	Published - 2018/12/01

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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, 9(1), Article 636. https://doi.org/10.1038/s41467-018-03038-w

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title = "Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood",

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.",

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

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doi = "10.1038/s41467-018-03038-w",

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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

TY - JOUR

T1 - Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

AU - Yuan, Xunmei

AU - Tsujimoto, Kazutaka

AU - Hashimoto, Koshi

AU - Kawahori, Kenichi

AU - Hanzawa, Nozomi

AU - Hamaguchi, Miho

AU - Seki, Takami

AU - Nawa, Makiko

AU - Ehara, Tatsuya

AU - Kitamura, Yohei

AU - Hatada, Izuho

AU - Konishi, Morichika

AU - Itoh, Nobuyuki

AU - Nakagawa, Yoshimi

AU - Shimano, Hitoshi

AU - Takai-Igarashi, Takako

AU - Kamei, Yasutomi

AU - Ogawa, Yoshihiro

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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JO - Nature Communications

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

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