Molecular mechanism of glycerophosphocholine metabolism and utilization as a choline supply
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
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | choline / ゲノム編集 / GDE5 / glycerophosphocholine / コリン / グリセロホスホコリン / liver / genome editing / GPC |
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.
|
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。
|
Report
(4 results)
Research Products
(19 results)
-
[Journal Article] GDE5 inhibition accumulates intracellular glycerophosphocholine and suppresses adipogenesis at a mitotic Clonal expansion stage2019
Author(s)
Okazaki Y, Nakamura K, Takeda S, Yoshizawa I, Yoshida F, Ohshima N, Izumi T, Klein JD, Kumrungsee T, Sands JM, Yanaka N.
-
Journal Title
American Journal of Physiology-Cell Physiology
Volume: 316
Issue: 2
Pages: C162-C174
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment2019
Author(s)
Kumrungsee T, Kariya T, Hashimoto K, Koyano T, Yazawa N, Hashimoto T, Sanada Y, Matsuyama M, Sotomaru Y, Sakurai H, Van de Loo F.A.J, Yanaka N
-
Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 14101-14101
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
[Journal Article] The effects of tempe fermented with Rhizopus microsporus, Rhizopus oryzae, or Rhizopus stolonifer on the colonic luminal environment in rats2018
Author(s)
Yang YS, Kameda T, Aoki H, Nirmagustina DE, Iwamoto A, Kato N, Yanaka N, Okazaki Y, Kumrungsee T.
-
Journal Title
J Funct Foods
Volume: 49
Pages: 162-167
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-