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Studies on molecular mechanisms of lipid accumulation in adipocytes for anti-metabolic syndrome

Research Project

Project/Area Number 19108002
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Food science
Research InstitutionThe University of Tokyo

Principal Investigator

SATO Ryuichiro  東京大学, 大学院・農学生命科学研究科, 教授 (50187259)

Co-Investigator(Kenkyū-buntansha) INOUE Jun  東京大学, 大学院・農学生命科学研究科, 講師 (70323962)
Project Period (FY) 2007 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥103,870,000 (Direct Cost: ¥79,900,000、Indirect Cost: ¥23,970,000)
Fiscal Year 2011: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2010: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2009: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2008: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2007: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Keywords脂肪細胞 / 脂肪滴 / トリグリセリド / メタボリックシンドローム / 抗肥満 / エネルギー / ペリリピン / ADRP / SREBP / コレステロール / 小胞体 / PPARγ / MEF / MLDP / 食品生化学 / RORα / TRC8 / ApoC-III / RXR / ROR / インスリン抵抗性 / TRB3 / 3T3-L1
Research Abstract

Adipocytes in adipose tissues store energy as triglycerides within lipid droplets and provide energy by degrading them when required. Excess storage of triglycerides in lipid droplets leads to obesity, which causes metabolic syndrome. To explore molecular mechanism of lipid droplet formation in adipocytes, molecular cell biological studies were carried out. We succeeded to identify a couple of novel factors that are deeply involved in lipid accumulation in adipocytes. Moreover, an assay system to evaluate the activity of food factors that increase energy expenditure in adipocytes was established. Using this system, a citrus limonoid was found to be a novel anti-obesity agent.

Report

(7 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (53 results)

All 2012 2011 2010 2009 2008 2007 Other

All Journal Article (25 results) (of which Peer Reviewed: 20 results) Presentation (21 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] HNF4αIncreases Liver-Specific Human ATP-Binding Cassette Transporter A1 Expression and Cholesterol Efflux to Apolipoprotein A-I in Response to Cholesterol Depletion2012

    • Author(s)
      Ohoka N, Okuhira K, Cui H, Wu W, Sato R, Naito N, and Nishimaki-Mogami T
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol

      Volume: 32 Issue: 4 Pages: 1005-1014

    • DOI

      10.1161/atvbaha.111.238360

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet2011

    • Author(s)
      Ono E, Inoue J, Hashidume T, Shimizu M, and Sato R
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 410 Pages: 677-681

    • URL

      http://dx.doi.org/10.1016/j.bbrc.2011.06.055

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glutamine stimulates the gene expression and processing of sterol regulatory element-binding proteins, thereby increasing the expression of their target genes2011

    • Author(s)
      Inoue J, Ito Y, Shimada S, Satoh S, Sasaki T, Hashidume T, Kamoshida Y, Shimizu M, and Sato R
    • Journal Title

      FEBS J

      Volume: 278 Issue: 15 Pages: 2739-2750

    • DOI

      10.1111/j.1742-4658.2011.08204.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of MIG12 as a mediator for stimulation of lipogenesis by LXR activation2011

    • Author(s)
      Inoue J, Yamasaki K, Ikeuchi E, Satoh, S, Fujiwara Y, Nishimaki-Mogami T, Shimizu M, and Sato R
    • Journal Title

      Mol. Endocrinol

      Volume: 25 Issue: 6 Pages: 995-1005

    • DOI

      10.1210/me.2011-0070

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] (*equalcontribution) Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1 and heat shock factor pathways2011

    • Author(s)
      Hatori,M.*, Hirota,T., Fukada,Y.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 108 Issue: 12 Pages: 4864-4869

    • DOI

      10.1073/pnas.1015959108

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The gene expression of the myocardial lipid droplet protein is highly regulated by PPARgamma in adipocytes differentiated from MEFs or SVCs2010

    • Author(s)
      Takahashi Y, Shinoda A, Inoue J, and Sato R
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 399 Pages: 209-214

    • URL

      http://dx.doi.org/10.1016/j.bbrc.2010.07.056

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Naringenin chalcone improves adipocyte functions by enhancing adiponectin production2010

    • Author(s)
      Horiba T, Nishimura I, Nakai Y, Abe K, and Sato R
    • Journal Title

      Mol. Cell. Endocrinol

      Volume: 323 Pages: 208-214

    • URL

      http://dx.doi.org/10.1016/j.mce.2010.03.020

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The gene expression of the myocardial lipid droplet protein is highly regulated by PPAR gamma in adipocytes differentiated from MEFs or SVCs.2010

    • Author(s)
      Takahashi, Y., Shinoda, A., Inoue, J., Sato, R.
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 399 Pages: 209-214

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Naringenin chalcone improves adipocyte functions by enhancing adiponectin production.2010

    • Author(s)
      Horiba, T., Nishimura, L, Nakai, Y., Abe, K., Sato, R.
    • Journal Title

      Mol.Cell.Endocrinol.

      Volume: 323 Pages: 208-214

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sterol-sensing ER membrane protein TRC8 hampers ER-to-Golgi transport of SREBP-2/SCAP and reduces SREBP-2 cleavage2009

    • Author(s)
      Irisawa M, Inoue J, Ozawa N, Mori K and Sato R
    • Journal Title

      J. Biol. Chem

      Volume: 284 Issue: 42 Pages: 28995-29004

    • DOI

      10.1074/jbc.m109.041376

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The orphan nuclear receptor RORαrestrains adipocyte differentiation through a reduction of C/EBPβactivity and perilipin gene expression2009

    • Author(s)
      Ohoka N, Kato S, Takahashi Y, Hayashi H, and Sato R
    • Journal Title

      Mol Endocrinol

      Volume: 23 Issue: 6 Pages: 759-771

    • DOI

      10.1210/me.2008-0277

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ApoC-III gene expression is sharply increased during adipogenesis and is augmented by retinoid X receptor(RXR) agonists2009

    • Author(s)
      Takahashi Y, Inoue J, Kagechika H and Sato R
    • Journal Title

      FEBS Lett

      Volume: 583 Pages: 493-497

    • URL

      http://dx.doi.org/10.1016/j.febslet.2008.12.050

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ApoC-III gene expression is sharply increased during adipogenesis and is augmented by retinoid X receptor (RXR) agonists2009

    • Author(s)
      Takahashi Y, Inoue J, Kagechika H, Sato R
    • Journal Title

      FEBS Lett. 583

      Pages: 493-497

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] The orphan nuclear receptor RORα restrains adipocyte differentiation through a reduction of C/EBPβ activity and perilipin gene expression2009

    • Author(s)
      Ohoka N, Kato S, Takahashi Y, Hayashi H, Sato R.
    • Journal Title

      Mol Endocrinol. 23

      Pages: 759-771

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] The sterol-sensing ER membrane protein TRC8 hampers ER-to-Golgi transport of SREBP-2/SCAP and reduces SREBP-2 cleavage2009

    • Author(s)
      Irisawa M, Inoue J, Ozawa N, Mori K, Sato R
    • Journal Title

      J.Biol.Chem. 284

      Pages: 28995-29004

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] The orphan nuclear receptor RORα restrains adipocyte differentiation through areduction of C/EBPβ activity and perilipin gene expression.2009

    • Author(s)
      Ohoka N, Kato S, Takahashi Y, Hayashi H, Sato R.
    • Journal Title

      Mol.Endocrinol. 23

      Pages: 759-771

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sterol-sensing ER membrane protein TRC8 hampers ER-to-Golgi transport of SREBP-2/SCAP and reduces SREBP-2 cleavage.2009

    • Author(s)
      Irisawa M, Inoue J, Ozawa N, Mori K, Sato R
    • Journal Title

      J.Biol.Chem. 284

      Pages: 28995-29004

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ApoC-IIIgeneexpressionissharplyincreasedduringadipogenesisandisaugmented by retinoid X receptor(RXR)agonists.2009

    • Author(s)
      Takahashi, Y., Inoue, J., Kagechika, H. and Satao, R.
    • Journal Title

      FEBS Letters 583

      Pages: 496-497

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The orphan nuclear receptor RORα restrains adipocyte differentiation through a reductionon of C/EBPβ activity and perihpin gene expression.2009

    • Author(s)
      Ohoka N, Kato S. Takahashi Y., Hayashi H, and Sato R.
    • Journal Title

      Mol Endocrinol (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PPARαgene expressionis up-regulated by LXR and PXR activators in the small intestine2008

    • Author(s)
      Inoue J, Satoh S, Kita M, Nakahara M, Hachimura S, Miyata M, Nishimaki-Mogami T and Sato R
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 371 Pages: 675-678

    • URL

      http://dx.doi.org/10.1016/j.bbrc.2008.04.100

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Growth factor-induced phosphorylation of sterol regulatory element-binding proteins inhibits sumoylation, thereby stimulating the expression of their target genes, low density lipoprotein uptake, and lipid synthesis2008

    • Author(s)
      Arito M, Horiba T, Hachimura S, Inoue J and Sato R
    • Journal Title

      J. Biol. Chem

      Volume: 283 Issue: 22 Pages: 15224-15231

    • DOI

      10.1074/jbc.m800910200

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRB3 suppresses adipocyte differentiation by negatively regulating PPARy transcriptional activity2008

    • Author(s)
      Takahashi Y, Ohoka N, Hayashi H and Sato R
    • Journal Title

      J. Lipid Res

      Volume: 49 Pages: 880-892

    • URL

      http://dx.doi.org/10.1016/j.bbrc.2010.07.056

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRB3 suppresses adipocyte differentiation by negatively regulating PPARγ transcriptional activity2008

    • Author(s)
      Takahashi Y, Ohoka N, Hayashi H, Sato R
    • Journal Title

      J.Lipid Res. 49

      Pages: 880-892

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Growth factor-induced phosphorylation of sterol regulatory element-binding proteins inhibits sumoylation, thereby stimulating the expression of their target genes, low density lipoprotein uptake, and lipid synthesis2008

    • Author(s)
      Arito M, Horiba T, Hachimura S, Inoue J, Sato R
    • Journal Title

      J.Biol.Chem. 283

      Pages: 15224-15231

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] TRB3 suppresses adipocyte differentiation by negatively regulating PPARγ transcriptional activity2008

    • Author(s)
      Takahashi Y, Ohoka N, Hayashi H, Sato R.
    • Journal Title

      J.Lipid Res 49

      Pages: 880-892

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Bel11bによる脂肪細胞分化制御機構の解析2012

    • Author(s)
      井原悠介, 神由美里、篠田旭弘、Shimizu Makoto、井上順、佐藤隆一郎
    • Organizer
      日本農芸化学会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Bcl11bによる脂肪細胞分化制御機構の解析日本農芸化学会2012

    • Author(s)
      井原悠介、神田美里、篠田旭弘、Shimizu Makoto、井上順、佐藤隆一郎
    • Organizer
      2012年度大会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪細胞内脂肪滴形成によるSREBP-1プロセシング促進2011

    • Author(s)
      篠田旭弘 高橋裕、井上 順、佐藤隆一郎
    • Organizer
      日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 脂肪細胞脂肪滴形成とSREBP活性化機構の分子基盤2011

    • Author(s)
      佐藤隆一郎
    • Organizer
      日本動物細胞工学会
    • Place of Presentation
      東京大学(招待講演)
    • Year and Date
      2011-07-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規LXR応答遺伝子の探索と機能解析2011

    • Author(s)
      井上順、山崎康平、池内江美奈、宮田慎吾、佐藤伸一、清水誠、佐藤隆一郎
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪細胞内脂肪滴形成によるSREBP-1プロセシング促進2011

    • Author(s)
      篠田旭弘、高橋裕、井上順、佐藤隆一郎
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of SREBP activation and sterol metabolism2010

    • Author(s)
      佐藤隆一郎
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      長良川国際会議場(岐阜県)
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂肪細胞における脂肪蓄積によるエネルギー代謝制御2010

    • Author(s)
      井上順、佐藤隆一郎
    • Organizer
      第64回日本栄養・食糧学会
    • Place of Presentation
      徳島
    • Year and Date
      2010-05-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪細胞における脂肪蓄積によるエネルギー代謝制御2010

    • Author(s)
      井上順、佐藤隆一郎
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      アスティ徳島(徳島県)
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂肪細胞における脂肪滴局在タンパク質ADRPの機能および分解機構解2010

    • Author(s)
      篠田旭弘, 高橋裕, 井上順, 佐藤隆一郎
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京、駒場
    • Year and Date
      2010-03-28
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 脂肪細胞における脂肪滴局在タンパク質ADRPの機能および分解機構解析2010

    • Author(s)
      篠田旭弘、高橋裕、井上順、佐藤隆一郎
    • Organizer
      日本農芸化学会
    • Place of Presentation
      東京・駒場
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脂肪細胞分化過程における核内受容体RORαの機能解析2009

    • Author(s)
      高橋裕, 大岡伸通, 加藤省吾, 林秀敏, 佐藤隆一郎
    • Organizer
      第30回日本肥満学会
    • Place of Presentation
      浜松
    • Year and Date
      2009-10-09
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 脂脂肪細胞分化過程における核内受容体RORα機能解析2009

    • Author(s)
      高橋裕, 大岡伸通, 加藤省吾、林秀敏、佐藤隆一郎
    • Organizer
      第30回日本肥満学会
    • Place of Presentation
      浜松
    • Year and Date
      2009-10-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脂質代謝調節に関する最近の話題2009

    • Author(s)
      佐藤隆一郎
    • Organizer
      第84回日本栄養・食糧学会関東支部会
    • Place of Presentation
      神奈川藤沢
    • Year and Date
      2009-09-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] フラボノイド類の核内受容体リガンド活性評価と脂質代謝改善効果2009

    • Author(s)
      佐藤隆一郎
    • Organizer
      日本農芸化学会2009年度大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Year and Date
      2009-03-27
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 新規脂肪細胞分化抑制因子の機能と栄養素2008

    • Author(s)
      佐藤隆一郎
    • Organizer
      日本肥満学会「第29回日本肥満学会」
    • Place of Presentation
      大分全日空ホテル・iichiko 総合文化センター
    • Year and Date
      2008-10-17
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 転写調節因子動脈硬化2008

    • Author(s)
      佐藤隆一郎
    • Organizer
      日本動脈硬化学会「第40回日本動脈硬化学会総会・学術集会」
    • Place of Presentation
      つくば国際会議場エポカルつくば : つくば市
    • Year and Date
      2008-07-10
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 脂肪細胞分化過程における脂肪滴局在タンパク質ADRPの機能解析2008

    • Author(s)
      篠田旭弘、高橋裕、渡辺英里、古屋徳彦、八村敏志、井上順、佐藤隆一郎
    • Organizer
      第31回日本分子生物学会年会/第81回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪細胞分化過程に伴うアポリポタンパク質apoC-IIIの発現誘導機構2008

    • Author(s)
      高橋裕、金山知彦、井上順、佐藤隆一郎
    • Organizer
      第31回日本分子生物学会年会/第81回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] グルタミンによる脂質代謝関連遺伝子調節因子SREBPの活性化機構の解明2008

    • Author(s)
      伊藤友香、島田聡子、佐藤伸一、八村敏志、井上順、佐藤隆一郎
    • Organizer
      第62回日本栄養・食糧学会大会
    • Place of Presentation
      埼玉
    • Related Report
      2011 Final Research Report
  • [Presentation] PPARγを介した転写調節による脂肪滴形成の制御2007

    • Author(s)
      高橋 裕, 大岡 伸通, 有村 直人, 林 秀敏, 佐藤 隆一郎
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Book] 生活習慣病の分子生物学2007

    • Author(s)
      佐藤隆一郎・今川正良
    • Total Pages
      156
    • Publisher
      三共出版
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://park.itc.u-tokyo.ac.jp/food-biochem/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://park.itc.u-tokyo.ac.jp/food-biochem/

    • Related Report
      2011 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://park.itc.u-tokyo.ac.jp/food-biochem/

    • Related Report
      2009 Self-evaluation Report
  • [Patent(Industrial Property Rights)] TGR5作動剤2012

    • Inventor(s)
      佐藤隆一郎・井上順・橋本修造・清水誠・中村明朗
    • Industrial Property Rights Holder
      佐藤隆一郎・井上順・橋本修造・清水誠・中村明朗
    • Filing Date
      2012-02-27
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] TGR5作動剤2010

    • Inventor(s)
      佐藤隆一郎・井上順・小野絵里
    • Industrial Property Rights Holder
      佐藤隆一郎・井上順・小野絵里
    • Filing Date
      2010-05-20
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 生体刺激存在下でmRNA のフレームシフトを利用した蛋白質の発現方法2010

    • Inventor(s)
      三浦正幸、岩脇隆夫
    • Industrial Property Rights Holder
      理化学研究所
    • Acquisition Date
      2010-01-29
    • Related Report
      2011 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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