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Exploration of novel pathway and genetic markers involved in dyslipidemia at post-GWAS era

Research Project

Project/Area Number 25461377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionJichi Medical University

Principal Investigator

Iwamoto Sadahiko  自治医科大学, 医学部, 教授 (10232711)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA KAZUHIRO  自治医科大学, 医学部, 講師 (90433581)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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
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.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (24 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] Mongolian National University(モンゴル)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Replication analysis of genetic association of the NCAN-CILP2 region with plasma lipid levels and non-alcoholic fatty liver disease in Asian and Pacific ethnic groups.2016

    • Author(s)
      Boonvisut S, Nakayama K, Makishima S, Watanabe K, Miyashita H, Lkhagvasuren M,Kagawa Y, Iwamoto S
    • Journal Title

      Lipids Health Dis.

      Volume: 15 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s12944-016-0181-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of TRIB1 in lipid metabolism; from genetics to pathways.2015

    • Author(s)
      Iwamoto S, Boonvisut S, Makishima S, Ishizuka Y, Watanabe K, Nakayama K
    • Journal Title

      Biochem Soc Trans.

      Volume: 43 Issue: 5 Pages: 1063-1068

    • DOI

      10.1042/bst20150094

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression.2015

    • Author(s)
      Makishima S, Boonvisut S, Ishizuka Y, Watanabe K, Nakayama K, Iwamoto S.
    • Journal Title

      J Lipid Res.

      Volume: 56 Issue: 6 Pages: 1145-1152

    • DOI

      10.1194/jlr.m057802

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients.2015

    • Author(s)
      Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata KI, et al.
    • Journal Title

      Brain Dev.

      Volume: 15 Issue: 1 Pages: 91-9

    • DOI

      10.1016/j.braindev.2015.04.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucagon directly interacts with vagal afferent nodose ganglion neurons to induce Ca(2+) signaling via glucagon receptors.2015

    • Author(s)
      Ayush EA, Iwasaki Y, Iwamoto S, Nakabayashi H, Kakei M, Yada T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 456 Issue: 3 Pages: 727-732

    • DOI

      10.1016/j.bbrc.2014.12.031

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis.2015

    • Author(s)
      Fujita-Jimbo E, Tanabe Y, Yu Z, Kojima K, Mori M, Li H, Iwamoto S, Yamagata T, Momoi MY, Momoi T.
    • Journal Title

      Mol Autism.

      Volume: 6 Issue: 1 Pages: 17-17

    • DOI

      10.1186/s13229-015-0012-5

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Common variants of GIP are associated with visceral fat accumulation in Japanese adults.2014

    • Author(s)
      Nakayama K, Watanabe K, Boonvisut S, Makishima S, Miyashita H, Iwamoto S.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol.

      Volume: 307 Issue: 11 Pages: G1108-G1114

    • DOI

      10.1152/ajpgi.00282.2014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      J Mol Endocrinol

      Volume: 52 Issue: 2 Pages: 145-158

    • DOI

      10.1530/jme-13-0243

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Seasonal effects of UCP1 gene polymorphism on visceral fat accumulation in Japanese adults2013

    • Author(s)
      Nakayama K, Miyashita H, Yanagisawa Y, Iwamoto S
    • Journal Title

      PLOS One

      Volume: 8 Issue: 9 Pages: e74720-e74720

    • DOI

      10.1371/journal.pone.0074720

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Genetic and functional assessment of rare alleles of NAFLD susceptibility loci in Japanese.2016

    • Author(s)
      Supichaya Boonvisut、Sadahiko Iwamoto, Nakayama Kazuhiro, Watanabe Kazuhisa
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都市左京区
    • Year and Date
      2016-04-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of population specific signals of positive election in Mongolians.2016

    • Author(s)
      Kazuhiro Nakayama, Jun Ohashi, Lkhagvasuren Munkhtulga, Sadahiko Iwamoto
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都市左京区
    • Year and Date
      2016-04-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Resequence analysis of NAFLD associated genes in 950 Japanese males2015

    • Author(s)
      Supichaya Boonvisut、渡邉和寿、中山一大、岩本禎彦
    • Organizer
      日本人類遺伝学会 第60回大会
    • Place of Presentation
      東京都新宿区
    • Year and Date
      2015-10-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 高密度SNPジェノタイピングによるモンゴル人特異的な自然選択の検出2015

    • Author(s)
      中山一大, 大橋順、ルハグワスレン・ムンフトルガ、岩本禎彦
    • Organizer
      第69回日本人類学会大会
    • Place of Presentation
      東京都江東区
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血清脂質関連遺伝子TRIB1の肝臓脂質レベル調節メカニズム2015

    • Author(s)
      岩本禎彦、巻嶋咲穂、Supichaya Boonvisut、渡邉和寿、中山一大
    • Organizer
      第36回日本肥満学会
    • Place of Presentation
      名古屋市熱田区
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析2015

    • Author(s)
      渡邉和寿、Supichaya Boonvisut、中山 一大、Leibel Rudolph、岩本 禎彦
    • Organizer
      第58回 日本糖尿病学会
    • Place of Presentation
      山口県下関市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Novel binding partners of TRIB1 involved in lipid metabolisms.2015

    • Author(s)
      Iwamoto S, Makishima S, Boonvisut S, Ishizuka Y, Watanabe K, Nakayama K
    • Organizer
      2015 tribbles meeting
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      2015-04-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Minor alleles of SNPs in NCAN-CILP2 region negatively affect on plasma triglyceride but positively on LDL in Japanese.2014

    • Author(s)
      S. Boonvisut, S. Makishima, K. Watanabe, K. Nakayama, S. Iwamoto.
    • Organizer
      日本人類遺伝学会 第59回大会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 多様な生活習慣を持つアジア・オセアニア人集団のゲノム情報の比較研究.2014

    • Author(s)
      中山一大、大橋順、Lhagvasuren Munkhtulga、香川靖雄、宮下洋、岩本禎彦.
    • Organizer
      日本人類遺伝学会 第59回大会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] A novel pathway involved in the susceptibility of non-alcoholic fatty liver diseases.2014

    • Author(s)
      S. Makishima, S. Boonvisut, K. Watanabe, K. Nakayama, S. Iwamoto.
    • Organizer
      64th Annual Meeting of American Society of Human Genetics.
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2014-10-18 – 2014-10-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Functional fine mapping of the responsible genes for plasma lipid regulation in the LD-block of NCAN/CILP2/PBX4 region.2014

    • Author(s)
      S. Boonvisut, S. Makishima, K. Watanabe, K. Nakayama, S. Iwamoto.
    • Organizer
      64th Annual Meeting of American Society of Human Genetics.
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2014-10-18 – 2014-10-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規肝臓脂質レベル調節分子の同定2013

    • Author(s)
      巻嶋咲穂、Supichaya Boonvisut、中山一大、森川千絵、岩本禎彦
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Functional screening of NCAN-CILP2 region for the genes involved in plasma lipid metabolism.2013

    • Author(s)
      Supichaya Boonvisut, Saho Makishima, Chie morikawa, Kazuhiro Nakayama, Iwamoto Sadahiko
    • Organizer
      日本人類遺伝学会 第58回大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] UCP1-3826G/A が内臓脂肪蓄積に及ぼす影響の季節性2013

    • Author(s)
      中山一大、宮下洋、岩本禎彦
    • Organizer
      日本人類遺伝学会 第58回大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2022-02-01  

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