Exploration of novel pathway and genetic markers involved in dyslipidemia at post-GWAS era
| Project/Area Number |
25461377
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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 |
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA KAZUHIRO 自治医科大学, 医学部, 講師 (90433581)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脂質代謝異常 / 非アルコール性脂肪肝 / SNP関連解析 / モデルマウス / 新規代謝パスウェイ / 分子間相互作用 / 遺伝環境相互作用 / 脂質異常症 / 遺伝的関連解析 |
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| Outline of Final Research Achievements |
Carbohydrate responsive element binding protein (ChREBP), a master regulator of hepatic lipogenesis, was identified as a novel binding partner of mammalian tribbles homologue 1 (TRIB1), the gene of which showed genetic association with plasma triglyceride levels. TRIB1 enhanced ChREBP proteolysis via ubiquitin-proteasome pathway. TRIB1 simultaneously enhanced mRNA expression of microsomal triglyceride transfer protein (MTTP), a principal molecule for VLDL secretion, via molecular interaction with Sin3A associated protein, 18kD. These two pathways may be involved in the genetic association of TRIB1 SNP in the enhancer element with plasma and hepatic lipid levels.
Furthermore, we discovered genetic association of Glucose-dependent insulinotropic polypeptide (GIP) with adiposity levels of visceral fat, which may be a predictive factor for the susceptibility to metabolic syndrome. We applied this result for a patent.
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions.2014
Author(s)
Ishizuka Y, Nakayama K, Ogawa A, Makishima S, Boonvisut S, Hirao A, Iwasaki Y, Yada T, Yanagisawa Y, Miyashita H, Takahashi M, Iwamoto S; Jichi Medical University Promotion Team of a Large-Scale Human Genome Bank for All over Japan
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Journal Title
J Mol Endocrinol
Volume: 52
Issue: 2
Pages: 145-158
DOI
Related Report
Peer Reviewed
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