Targeting DNA methylation for the treatment of obesity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21745
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Gunma University
• Principal Investigator: Kohno Daisuke 群馬大学, 生体調節研究所, 助教 (10382904)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 肥満 / 視床下部 / DNAメチル化修飾 / エピゲノム編集 / チロシン水酸化酵素

Outline of Final Research Achievements

We previously reported that aberrant regulation of DNA methylation in the paraventricular nucleus of the hypothalamus strongly affects tyrosine hydroxylase (Th) gene expression and induces obesity. In this study, we aimed to artificially manipulate the level of DNA methylation of the Th gene in the hypothalamus using epigenome editing. First, we studied using cultured cells and were able to reduce the level of DNA methylation of the Th promoter. We used lipid nanoparticles (LNP) to transfect the plasmid DNA vector into the mouse brain. However, we have not been able to complete our testing of delivery conditions to induce sufficient changes. We will continue this project to achieve this goal.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

DNAメチル化修飾の操作によるドーパミン発現の調節は、肥満だけではなく、ドーパミンにかかわる複数の病気の治療につながるものであり、行う意義は高い。また、DNAメチル化修飾を標的とすることで、発現を単純に増加や抑制するのではなく、発現のされやすさに影響を与えて穏やか発現を変化させることが期待できる。また、DNAメチル化修飾の操作を中枢の特定のニューロン群で行うことは、技術的に容易ではないが、本研究を通して改善方法の検討を行うことができた。今後もこの課題を継続し、成功させて学術的、社会的に有意義なものにしたい。