Analysis of epigenetic memory of FGF21 gene in the liver
| Project/Area Number |
26350884
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Yuan Xunmei 東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (70392404)
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| Co-Investigator(Renkei-kenkyūsha) |
HASHIMOTO Koshi 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30396642)
OGAWA Yoshihiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70291424)
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| Research Collaborator |
TSUJIMOTO Kazutaka
KAWAHORI Kenichi
HANZAWA Nozomi
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | PPARα / FGF21 / DOHaD / エピジェネティックメモリー / DNAメチル化 / DNA脱メチル化 / エピゲノム記憶 / エピゲノム制御 / DOHaD仮説 / エピジェネティクス / 先制医療 |
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| Outline of Final Research Achievements |
Nutritional experiences in early life may be stored onto the genome, thereby influencing the risk of obesity in later life. However, the detailed mechanism is poorly understood. In this study, we demonstrated that PPARα8211;dependent DNA demethylation of the FGF21 gene occurs in the postnatal mouse liver. Moreover, DNA demethylation of FGF21 gene can be modulated and enhanced by pharmacologic activation of PPARα, specifically during the suckling period. Of note, the DNA methylation status of FGF21 gene, once established in early life, is relatively stable and persists into adulthood, which can be referred to as epigenetic memory. When DNA demethylation has been markedly induced, hepatic induction of FGF21 expression is exaggerated upon PPARα activation, which may account in part for the attenuation of diet-induced obesity in adulthood. Thus, we propose that FGF21 could be a key mediator involved in the developmental programming of obesity.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Ligand-activated PPARα-dependent DNA demethylation regulates the fatty acid β-oxidation genes in the postnatal liver.2015
Author(s)
Ehara T, Kamei Y, Yuan X, Takahashi M, Kanai S, Tamura E, Tsujimoto K, Tamiya T, Nakagawa Y, Shimano H, Takai-Igarashi T, Hatada I, Suganami T, Hashimoto K, Ogawa Y.
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Journal Title
Diabetes
Volume: 64(3)
Pages: 775-784
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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