Molecular mechanism of glycerophosphocholine metabolism and utilization as a choline supply

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07757
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: YANAKA Noriyuki 広島大学, 統合生命科学研究科(生), 准教授 (70346526)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: choline / ゲノム編集 / GDE5 / glycerophosphocholine

Outline of Final Research Achievements

Choline is an essential nutrient for the de novo synthesis of cell membrane phospholipid PC, methyl donor betaine, and neurotransmitter acetylcholine. It is well-known that choline deficiency causes various diseases such as fatty liver, whereas the nutritional importance of choline is under-recognized. Here, I tried to generate GDE5 KO mouse model using CRISPR-Cas9 genome editing to show the involvement of GDE5 in choline synthesis in vivo and the nutritional importance of choline in a tissue-specific manner. In this study, I established liver-specific GDE5-deficient mice and showed that GPC was accumulated and betaine level was decreased. Also, S-adenocylmethionine, a major methyl donor, was decreased and, in contrast, S-adenocylhomocysteine was increased. This study firstly demonstrated that GDE5 has an important function in choline synthetic pathway and plays roles in methyl group metabolism in vivo.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究では、GDE5のcholine供給に果たす役割をin vivoで初めて実証するとともに、標的組織特異的にcholine代謝を変動させ、同組織でのcholine代謝の重要性を検証する手法として利用されるものである。特に、肝臓組織特異的なcholine欠乏による肝障害を誘導するためには、choline欠乏食による長期の飼育が必要であると考えられているが、GDE5のcholine供給を遮断するマウスモデルとして利用することによって、より詳細なcholineの栄養学的重要性を提示しえるものと期待される。