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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042010597&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03038-w
DO - 10.1038/s41467-018-03038-w
M3 - 学術論文
C2 - 29434210
AN - SCOPUS:85042010597
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 636
ER -