Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood
| Autor: | Izuho Hatada, Nozomi Hanzawa, Hitoshi Shimano, Yasutomi Kamei, Kenichi Kawahori, Koshi Hashimoto, Tatsuya Ehara, Yoshimi Nakagawa, Makiko Nawa, Nobuyuki Itoh, Xunmei Yuan, Takami Seki, Takako Takai-Igarashi, Miho Hamaguchi, Kazutaka Tsujimoto, Morichika Konishi, Yoshihiro Ogawa, Yohei Kitamura |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty FGF21 Science General Physics and Astronomy Peroxisome proliferator-activated receptor Biology General Biochemistry Genetics and Molecular Biology Article Epigenesis Genetic 03 medical and health sciences Mice Internal medicine medicine Animals Humans PPAR alpha Epigenetics Obesity lcsh:Science Epigenesis Regulation of gene expression chemistry.chemical_classification Multidisciplinary General Chemistry Methylation DNA Methylation Diet Fibroblast Growth Factors 030104 developmental biology Endocrinology DNA demethylation chemistry Gene Expression Regulation Liver DNA methylation Hepatocytes Female lcsh:Q |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03038-w |
| Popis: | 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. FGF21 exerts beneficial metabolic effects on multiple tissues. Here the authors show that the Fgf21 gene is demethylated during the postnatal suckling period, creating an epigenetic memory that determines the responsiveness of the Fgf21 gene to inducers such as PPARα activators or fasting in adulthood. |
| Databáze: | OpenAIRE |
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