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
N1 - Funding Information:
We thank Ms. Rie Yamada and Ms. Yumi Gotoda for secretarial assistance and Drs. Mayumi Takahashi (Osaka Women’s Junior College) and Yoshiaki Nakayama (Kobe Pharmaceutical University) for technical assistance. We also thank Dr. Toshiya Tanaka (Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Japan) for providing anti-PPARα antibody. This work was supported in part by Grants-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science [grant numbers JP16H05331 (Y.O.), JP16H01354 (Y.O.), JP26461376 (K.H.), and JP26350884 (X.Y.)]; Secom Science and Technology Foundation (Y.O.); The Naito Foundation (Y.O.), Nestlé Nutrition Council (X.Y.), Japan; Takeda Science Foundation (K.H.); Dairy Products Health Science Council of Japan Milk Academic Alliance (K.H.); and Tohoku Medical Megabank Project (T.T.-I.).
Publisher Copyright:
© 2018 The Author(s).
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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U2 - 10.1038/s41467-018-03038-w
DO - 10.1038/s41467-018-03038-w
M3 - Article
C2 - 29434210
AN - SCOPUS:85042010597
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 636
ER -
