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 and Yoshihiro Ogawa ()
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Xunmei Yuan: 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
Takami Seki: Tokyo Medical and Dental University
Makiko Nawa: Tokyo Medical and Dental University
Tatsuya Ehara: Tokyo Medical and Dental University
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
Hitoshi Shimano: University of Tsukuba
Takako Takai-Igarashi: Tohoku Medical Megabank Organization
Yasutomi Kamei: Kyoto Prefectural University
Yoshihiro Ogawa: Tokyo Medical and Dental University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03038-w

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