Genetic and environmental factors related to onset and severity of CTLN2 in citrin deficiency
| Project/Area Number |
15K09595
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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 |
Pediatrics
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| Research Institution | Kagoshima University |
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Principal Investigator |
Saheki Takeyori 鹿児島大学, 医歯学総合研究科, 客員研究員 (10056070)
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| Co-Investigator(Kenkyū-buntansha) |
井ノ上 逸朗 国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500)
矢崎 正英 信州大学, 学術研究院保健学系, 教授 (70372513)
森山 光章 大阪府立大学, 生命環境科学研究科, 准教授 (20275283)
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| Research Collaborator |
FUNAHASHI Aki 鹿児島大学, 医歯学総合研究科
KURODA Eishi 鹿児島大学, 医歯学総合研究科
YASUDA Izumi 鹿児島大学, 医歯学総合研究科
SETOGAWA Yoshiko 鹿児島大学, 医歯学総合研究科
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | citrin deficiency / CTLN2 / hyperammonemia / sugar toxicity / NADH / ornithine / aspartate / alanine / シトリン欠損症モデルマウス / 高アンモニア血症 / 糖質の毒性 / アミノ酸の効果 / ショ糖摂取 / 忌避 / アミノ酸 / 滅菌餌 / 修飾遺伝子 / 尿素サイクル酵素 / 成長障害 |
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| Outline of Final Research Achievements |
Aversion against sugars is the remarkable characteristics of citrin deficiency. We showed that two factors simultaneously induced by sugar intake, an increased cytosolic NADH and decreased ATP in the liver, send signals to the brain, to avoid intake of excess sugars.
On the other hand, we have shown that intake of protein and some amino acids ameliorate sugar toxicity. In this research, we clarified that a severe hyperammonemia induced in the model mice was greatly relieved by oral administration of ornithine + aspartate or alanine. Although aspartate can’t directly enter the hepatocyte carrying urea cycle, it can be converted into alanine in the small intestine, which then can enter the hepatocyte with urea cycle and converted back to aspartate, resulting in almost complete dissolution of hyperammonemia.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency2017
Author(s)
Saheki T, Inoue K, Ono H, Fujimoto Y, Furuie S, Yamamura KI, Kuroda E, Ushikai M, Asakawa A, Inui A, Eto K, Kadowaki T, Moriyama M, Sinasac DS, Yamamoto T, Furukawa T, Kobayashi K.
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Journal Title
Mol. Genet. Metab.
Volume: 120
Pages: 306-316
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.2017
Author(s)
Saheki T, Inoue K, Ono H, Fujimoto Y, Furuie S, Yamamura KI, Kuroda E, Ushikai M, Asakawa A, Inui A, Eto K, Kadowaki T, Moriyama M, Sinasac DS, Yamamoto T, Furukawa T, Kobayashi K.
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Journal Title
Mol Genet Metab.
Volume: 120
Pages: 306-316
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment.2017
Author(s)
Nagasaka H, Komatsu H, Inui A, Nakacho M, Morioka I, Tsukahara H, Kaji S, Hirayama S, Miida T, Kondou H, Ihara H, Yagi M, Kizaki Z, Bessho K, Kodama T, Iijima K, Saheki T, Yorifuji T, Honda A
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Journal Title
Mol Genet Metab
Volume: 120
Pages: 207-212
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mechanism for increased hepatic glycerol synthesis in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse : Urine glycerol and glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency.2015
Author(s)
Moriyama M, Fujimoto Y, Rikimaru S, Ushikai M, Kuroda E, Kawabe K, Takano K, Asakawa A, Inui A, Eto K, Kadowaki T, …, Kure S, Mitsubuchi H, Endo F, Horiuchi M, Nakamura Y, Yamamura K, Saheki T
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Journal Title
BBA Molecular Basis of Disease
Volume: 印刷中
Pages: 1787-1795
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Pathogenesis, Pathophysiology and Treatment of Citrin Deficiency, -Treatment of Hyperammonemia in Citrin Deficiency with Amino Acids by using the Model, Citrin/mGPD double-KO, Mice-2017
Author(s)
Saheki T, Kuroda E, Funahashi A, Yasuda I, Setogawa Y, Gao GH, Ushikai M, Horiuchi M, Moriyama M
Organizer
International Congress on Inborn Error of Metabolism (ICIEM) 2017
Related Report
Int'l Joint Research / Invited
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