Analysis of epigenetic memory of FGF21 gene in the liver

2016 Fiscal Year Final Research Report

• Project/Area Number: 26350884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Tokyo Medical and Dental University
• 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)
• 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)
• Research Collaborator: TSUJIMOTO Kazutaka ; KAWAHORI Kenichi ; HANZAWA Nozomi
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

応用健康科学