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Mechanism and prevention strategy of inflammation and fibrosis caused by quantitative and qualitative transformation of organ lipids in inflammation cellular society

Planned

Project AreaPreventive medicine through inflammation cellular sociology
Project/Area Number 17H06395
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionUniversity of Tsukuba

Principal Investigator

島野 仁  筑波大学, 医学医療系, 教授 (20251241)

Co-Investigator(Kenkyū-buntansha) 松坂 賢  筑波大学, 医学医療系, 教授 (70400679)
中川 嘉  筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
Project Period (FY) 2017-06-30 – 2022-03-31
Project Status Granted (Fiscal Year 2021)
Budget Amount *help
¥91,520,000 (Direct Cost: ¥70,400,000、Indirect Cost: ¥21,120,000)
Fiscal Year 2021: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2017: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
KeywordsscRNA-seq / 膵ラ氏島 / 糖尿病 / 脂質代謝 / SREBP-1 / 脂質 / 炎症 / 線維化 / 異質 / 膵臓ラ氏島 / NASH / 未病 / 1細胞解析 / 生活習慣病 / 慢性炎症 / 非アルコール性脂肪肝 / CREBH / ChREBP / 動脈硬化 / Elovl6 / SREBP / 肥満 / 発現制御
Outline of Annual Research Achievements

2型糖尿病の発症過程における膵島の炎症細胞社会の変遷を、scRNA-seqを駆使して網羅的に把握し、新規のメカニズムを知ることが本研究の主題の一つである。健常から未病状態、未病状態から糖尿病発症へ進展するときの膵島の個々の細胞の変化を明らかにすることを目的として、2型糖尿病モデルマウスであるdb/dbマウスの膵島のscRNA-seq解析を行った。その結果、正常、糖尿病発症初期、糖尿病状態の膵島の細胞がβ細胞、α細胞、δ細胞、PP細胞、マクロファージ、血管内皮細胞など20種類のクラスターに分類された。また、β細胞は病態の進行に伴い9種類のクラスターに分類され、機能エンリッチメント解析から糖尿病の進行に伴い変化する複数のパスウェイが見出された。さらに、scRNA-seqにより糖尿病発症初期のβ細胞で特異的に発現が増加する遺伝子Xを同定し、現在その発現誘導メカニズムおよびβ細胞における機能の解析を行っている。これらの知見は、2型糖尿病の発症機序の解明や新規バイオマーカーの発見および治療法開発に寄与すると期待される。
肝臓の脂質代謝と炎症、線維化の関連を探索する目的で実施している新規プロテアーゼ(R4)によるSREBP-1活性化制御機構の解析では、ウェスタンダイエット(WD)2週間負荷による肥満誘発マウスの解析を行った。WD負荷により、野生型、R4 KOマウス共に体重と脂肪組織の増加が見られたが、体重や肝重量の有意な差は見られなかった。しかし、R4 KOでは、脂肪組織量、血中トリグリセリド、肝臓の総脂肪酸量が低下していた。また、脂肪酸組成解析の結果、多価不飽和脂肪酸種の減少傾向が見られた。R4 KOマウス肝臓では、de novo lipogenesisや多価不飽和脂肪酸の合成酵素の遺伝子発現も低下していることから、R4-SREBP-1経路による脂肪酸合成制御を示すことができた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

2型糖尿病モデルマウスの膵島のscRNA-seqに成功し、糖尿病の発症過程におけるβ細胞の遺伝子発現の変遷や多様性を確認することが出来た。また、糖尿病発症初期のβ細胞で特異的に発現が上昇する遺伝子を見出し、新規糖尿病発症予測マーカーあるいは糖尿病の治療標的として期待される。
肝臓のSREBP-1の脂肪酸種特異的プロテアーゼの発見に関する研究は論文として投稿準備中である。新規プロテアーゼ(R4)は、既存のSREBP-1切断活性化経路とは異なり、ゴルジ体への輸送を介さずにER膜上でSREBP-1と共局在、相互作用し、SREBP-1を切断、活性化することを明らかにした。また、SREBP-1活性化の既存経路がコレステロールにより制御されるのに対し、R4-SREBP-1経路は、脂肪酸種により制御-飽和脂肪酸により活性化、不飽和脂肪酸により抑制-されることをin vitro及びin vivoの系で示すことができた。さらに、R4-SREBP-1経路によるde novo lipogenesisや多価不飽和脂肪酸合成系の活性化を示すことができ、新たなR4-SREBP-1経路による脂質代謝制御機構を提唱することができた。

Strategy for Future Research Activity

糖尿病発症初期のβ細胞で特異的に発現が増加する遺伝子Xと糖尿病との関係を、scRNA-seqのデータ解析および培養細胞を用いた機能解析により明らかにする。
新規プロテアーゼ(R4)によるSREBP-1活性化制御機構の解析では、炎症・線維化との関連を明らかにする。我々はこれまでの研究で、ウェスタンダイエット(WD)2週間負荷による肥満誘発マウスの解析からR4-SREBP-1経路による脂質代謝制御を明らかにすることができた。今後は、長期間のWD負荷により、NAFLD誘発マウスを作製し、解析を進める。NAFLD病態が確認できたマウスの血液や肝臓の脂質及び炎症パラメーターを評価する。また、肝臓組織の脂質沈着や炎症進行を病理切片の作製・免疫組織染色を行い解析する。さらに、肝臓組織の脂肪酸組成解析や、遺伝子発現解析を行い、網羅的な脂質変動と遺伝子発現変動を把握することでR4-SREBP-1経路によるNAFLD病態のメカニズムを探っていく。

Report

(4 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(56 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (32 results) (of which Int'l Joint Research: 20 results,  Peer Reviewed: 32 results,  Open Access: 27 results) Presentation (20 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan2021

    • Author(s)
      Tateishi R、Matsumura T、Okanoue T、Shima T、Uchino K、Fujiwara N、Senokuchi T、Kon K、Sasako T、Taniai M、Kawaguchi T、Inoue H、Watada H、Kubota N、Shimano H、Kaneko S、Hashimoto E、Watanabe S、Shiota G、Ueki K、Kashiwabara K、Matsuyama Y、Tanaka H、Kasuga M、Araki E、Koike K
    • Journal Title

      J Gastroenterol.

      Volume: 56 Pages: 261-273

    • DOI

      10.1007/s00535-020-01754-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enterohepatic Transcription Factor CREB3L3 Protects Atherosclerosis via SREBP Competitive Inhibition2021

    • Author(s)
      Nakagawa Yoshimi、Wang Yunong、Han Song-iee、Okuda Kanako、Oishi Asayo、Yagishita Yuka、Kumagai Kae、Ohno Hiroshi、Osaki Yoshinori、Mizunoe Yuhei、Araki Masaya、Murayama Yuki、Iwasaki Hitoshi、Konishi Morichika、Itoh Nobuyuki、Matsuzaka Takashi、Sone Hirohito、Yamada Nobuhiro、Shimano Hitoshi
    • Journal Title

      Cell Mol Gastroenterol Hepatol.

      Volume: 11 Pages: 949-971

    • DOI

      10.1016/j.jcmgh.2020.11.004

    • NAID

      120006939158

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non‐alcoholic steatohepatitis model2021

    • Author(s)
      Shimizu Yoshio、Tamura Takafumi、Kemmochi Akira、Owada Yohei、Ozawa Yusuke、Hisakura Katsuji、Matsuzaka Takashi、Shimano Hitoshi、Nakano Noriyuki、Sakashita Shingo、Oda Tatsuya、Ohkohchi Nobuhiro
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 36 Pages: 800-810

    • DOI

      10.1111/jgh.15239

    • NAID

      120007165441

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guidelines on the Clinical Evaluation of Medicinal Products for Treatment of Dyslipidemia2020

    • Author(s)
      Yamashita Shizuya、Kouji Kajinami, et al.
    • Journal Title

      J Atheroscler Thromb

      Volume: 27 Issue: 11 Pages: 1246-1254

    • DOI

      10.5551/jat.cr004

      10.5551/jat.CR004

    • NAID

      130007933950

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Srebp-1c/Fgf21/Pgc-1α Axis Regulated by Leptin Signaling in Adipocytes?Possible Mechanism of Caloric Restriction-Associated Metabolic Remodeling of White Adipose Tissue2020

    • Author(s)
      Kobayashi Masaki、Uta Seira、Otsubo Minami、Deguchi Yusuke、Tagawa Ryoma、Mizunoe Yuhei、Nakagawa Yoshimi、Shimano Hitoshi、Higami Yoshikazu
    • Journal Title

      Nutrients

      Volume: 12 Pages: 2054-2054

    • DOI

      10.3390/nu12072054

    • NAID

      120007147861

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new perspective on type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease.2020

    • Author(s)
      Matsuzaka T, Shimano H.
    • Journal Title

      Journal of Diabetes Investigation

      Volume: in press Pages: 532-534

    • DOI

      10.1111/jdi.13258

    • NAID

      120007165450

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deciphering genetic signatures by whole exome sequencing in a case of co-prevalence of severe renal hypouricemia and diabetes with impaired insulin secretion2020

    • Author(s)
      Sekiya Motohiro、Matsuda Takaaki、Yamamoto Yuki、Furuta Yasuhisa、Ohyama Mariko、Murayama Yuki、Sugano Yoko、Ohsaki Yoshinori、Iwasaki Hitoshi、Yahagi Naoya、Yatoh Shigeru、Suzuki Hiroaki、Shimano Hitoshi
    • Journal Title

      BMC Medical Genetics

      Volume: 21 Pages: 91-91

    • DOI

      10.1186/s12881-020-01031-z

    • NAID

      120007147873

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms2020

    • Author(s)
      Satoh A, Han S, Araki M, Nakagawa Y, Ohno H, Mizunoe Y, Kumagai K, Murayama Y, Osaki Y, Iwasaki H, Sekiya M, Konishi M, Itoh N, Matsuzaka T, Sone H, and Shimano H.
    • Journal Title

      iScience

      Volume: 23 Issue: 3 Pages: 100930-100930

    • DOI

      10.1016/j.isci.2020.100930

    • NAID

      120006891020

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice2020

    • Author(s)
      Matsuzaka T, Kuba M, Koyasu S, Takeuchi Y, Yahagi N, Miyamoto T, Sekiya M, Nakagawa Y, Ema M, Takahashi S, Tokiwa H, Shimano H.
    • Journal Title

      Hepatology

      Volume: 71 Pages: 1609-1625

    • DOI

      10.1002/hep.30953

    • NAID

      120007132717

    • Description
      in press
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Handgrip strength predicts new prediabetes cases among adults: A prospective cohort study2020

    • Author(s)
      Manda Chrispin Mahala、Hokimoto Takahiro、Okura Tomohiro、Isoda Hiroko、Shimano Hitoshi、Wagatsuma Yukiko
    • Journal Title

      Preventive Medicine Reports

      Volume: 17 Pages: 101056-101056

    • DOI

      10.1016/j.pmedr.2020.101056

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cathepsin B overexpression induces degradation of perilipin 1 to cause lipid metabolism dysfunction in adipocytes2020

    • Author(s)
      Mizunoe Yuhei、Kobayashi Masaki、Hoshino Shunsuke、Tagawa Ryoma、Itagawa Rei、Hoshino Ayana、Okita Naoyuki、Sudo Yuka、Nakagawa Yoshimi、Shimano Hitoshi、Higami Yoshikazu
    • Journal Title

      Sci Rep.

      Volume: 10 Pages: 634-634

    • DOI

      10.1038/s41598-020-57428-6

    • NAID

      120007165462

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of Molecular Mechanism of a Selective PPARα Modulator, Pemafibrate, through Combinational Approaches of X-ray Crystallography, Thermodynamic Analysis, and First-Principle Calculations2020

    • Author(s)
      Kawasaki Mayu、Kambe Akira、Yamamoto Yuta、Arulmozhiraja Sundaram、Ito Sohei、Nakagawa Yoshimi、Tokiwa Hiroaki、Nakano Shogo、Shimano Hitoshi
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Pages: 361-361

    • DOI

      10.3390/ijms21010361

    • NAID

      120007132701

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptional co-repressor CtBP2 orchestrates epithelial-mesenchymal transition through a novel transcriptional holocomplex with OCT12020

    • Author(s)
      Ma Yang、Sekiya Motohiro、Kainoh Kenta、Matsuda Takaaki、Iwasaki Hitoshi、Osaki Yoshinori、Sugano Yoko、Suzuki Hiroaki、Takeuchi Yoshinori、Miyamoto Takafumi、Yahagi Naoya、Nakagawa Yoshimi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 523 Pages: 354-360

    • DOI

      10.1016/j.bbrc.2019.12.070

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome2019

    • Author(s)
      Mizunoe Yuhei、Kobayashi Masaki、Tagawa Ryoma、Nakagawa Yoshimi、Shimano Hitoshi、Higami Yoshikazu
    • Journal Title

      Int J Mol Sci.

      Volume: 20 Pages: 3688-3688

    • DOI

      10.3390/ijms20153688

    • NAID

      120007133171

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential2019

    • Author(s)
      Fruchart Jean-Charles、Santos Raul D.Ponte-Negretti Carlos I、Pradhan Aruna、Ray Kausik K.、Reiner ?eljko、Ridker Paul M.、Ruscica Massimiliano、Sadikot Shaukat、Shimano Hitoshi. et al
    • Journal Title

      Cardiovasc Diabetol.

      Volume: 18 Pages: 71-71

    • DOI

      10.1186/s12933-019-0864-7

    • NAID

      120007133397

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rho‐associated, coiled‐coil‐containing protein kinase?1 as a new player in the regulation of hepatic lipogenesis2019

    • Author(s)
      Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      J Diabetes Investig.

      Volume: 10 Pages: 1165-1167

    • DOI

      10.1111/jdi.13051

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism2019

    • Author(s)
      Sharma Rahu, Takafumi Miyamoto, et al.
    • Journal Title

      Sci Rep

      Volume: 9 Pages: 1-12

    • DOI

      10.1038/s41598-019-41631-1

    • NAID

      120007133465

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptome network analysis identifies protective role of the LXR/SREBP-1c axis in murine pulmonary fibrosis.2019

    • Author(s)
      Shichino S, Ueha S, Hashimoto S, Otsuji M, Abe J, Tsukui T, Deshimaru S, Nakajima T, Kosugi-Kanaya M, Shand FH, Inagaki Y, Shimano H, Matsushima K.
    • Journal Title

      JCI Insight

      Volume: 4(1) Pages: 122163-122163

    • DOI

      10.1172/jci.insight.122163

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation.2018

    • Author(s)
      Nakamura Y, Matsuzaka T, Tahara-Hanaoka S, Shibuya K, Shimano H, Nakahashi-Oda C, Shibuya A.
    • Journal Title

      Cell Death and Diseases

      Volume: 9(12) Pages: 1181-1181

    • DOI

      10.1038/s41419-018-1226-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Peroxisome Proliferator-Activated Receptor α (PPARα) Agonist Pemafibrate Protects against Diet-Induced Obesity in Mice2018

    • Author(s)
      Araki Masaya、Nakagawa Yoshimi、Oishi Asayo、Han Song-iee、Wang Yunong、Kumagai Kae、Ohno Hiroshi、Mizunoe Yuhei、Iwasaki Hitoshi、Sekiya Motohiro、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      International journal of molecular sciences

      Volume: 19 Pages: 2148-2148

    • DOI

      10.3390/ijms19072148

    • NAID

      120007133834

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance.2018

    • Author(s)
      Ohno H, Matsuzaka T, Tang N, Sharma R, Motomura K, Shimura T, Satoh A, Han SI, Takeuchi Y, Aita Y, Iwasaki H, Yatoh S, Suzuki H, Sekiya M, Nakagawa Y, Sone H, Yahagi N, Yamada N, Higami Y, Shimano H.
    • Journal Title

      Endocrinology

      Volume: 159(6) Pages: 2308-2323

    • DOI

      10.1210/en.2017-03179

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular association model of PPARα and its new specific and efficient ligand, pemafibrate: Structural basis for SPPARMα2018

    • Author(s)
      Yamamoto Yuta、Takei Kenta、Arulmozhiraja Sundaram、Sladek Vladimir、Matsuo Naoya、Han Song-iee、Matsuzaka Takashi、Sekiya Motohiro、Tokiwa Takaki、Shoji Mitsuo、Shigeta Yasuteru、Nakagawa Yoshimi、Tokiwa Hiroaki、Shimano Hitoshi
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 499 Pages: 239-245

    • DOI

      10.1016/j.bbrc.2018.03.135

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in MacrophagesHighlights2018

    • Author(s)
      Karasawa Tadayoshi、Kawashima Akira、Usui-Kawanishi Fumitake、Watanabe Sachiko、Kimura Hiroaki、Kamata Ryo、Shirasuna Koumei、Koyama Yutaro、Sato-Tomita Ayana、Matsuzaka Takashi、Tomoda Hiroshi、Park Sam-Yong、Shibayama Naoya、Shimano Hitoshi、Kasahara Tadashi、Takahashi Masafumi
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 38 Pages: 744-756

    • DOI

      10.1161/atvbaha.117.310581

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood2018

    • Author(s)
      X Yuan, K Tsujimoto, K Hashimoto, K Kawahori, N Hanzawa, M Hamaguchi, T Seki, M Nawa, T Ehara, Y Kitamura, I Hatada, M Konishi, N Itoh, Y Nakagawa, H Shimano, T Takai-Igarashi, Y Kamei, Y Ogawa.
    • Journal Title

      Nat. Commun.

      Volume: 9 Pages: 636-636

    • DOI

      10.1038/s41467-018-03038-w

    • NAID

      120007134467

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood.2018

    • Author(s)
      Yuan X, Tsujimoto K, Hashimoto K, Kawahori K, Hanzawa N, Hamaguchi M, Seki T, Nawa M, Ehara T, Kitamura Y, Hatada I, Konishi M, Itoh N, Nakagawa Y, Shimano H, Takai-Igarashi T, Kamei Y, Ogawa Y.
    • Journal Title

      Nat Commun.

      Volume: 9(1) Pages: 636-636

    • NAID

      120007134467

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes.2018

    • Author(s)
      Piao X, Yahagi N, Takeuchi Y, Aita Y, Murayama Y, Sawada Y, Shikama A, Masuda Y, Nishi-Tatsumi M, Kubota M, Izumida Y, Sekiya M, Matsuzaka T, Nakagawa Y, Sugano Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Shimano H.
    • Journal Title

      FEBS Letters

      Volume: 592(3) Pages: 422-433

    • DOI

      10.1002/1873-3468.12975

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel non-alcoholic steatohepatitis model with histopathological and insulin-resistant features.2018

    • Author(s)
      Owada Y, Tamura T, Tanoi T, Ozawa Y, Shimizu Y, Hisakura K, Matsuzaka T, Shimano H, Nakano N, Sakashita S, Matsukawa T, Isoda H, Ohkohchi N.
    • Journal Title

      Pathol Int.

      Volume: 68(1) Pages: 12-22

    • DOI

      10.1111/pin.12612

    • NAID

      120007134624

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of CREBH-mediated induction of transforming growth factor β2 by hepatitis C virus infection in fibrogenic responses in hepatic stellate cells2018

    • Author(s)
      Chida Takeshi、Ito Masahiko、Nakashima Kenji、Kanegae Yumi、Aoshima Takuya、Takabayashi Shuji、Kawata Kazuhito、Nakagawa Yoshimi、Yamamoto Masahiro、Shimano Hitoshi、Matsuura Tomokazu、Kobayashi Yoshimasa、Suda Takafumi、Suzuki Tetsuro
    • Journal Title

      Hepatology.

      Volume: 66 Pages: 1430-1443

    • DOI

      10.1002/hep.29319

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mitochondrial intermediate peptidase is a novel regulator of sirtuin-3 activation by caloric restriction2017

    • Author(s)
      Kobayashi Masaki、Takeda Kanae、Narita Takumi、Nagai Keita、Okita Naoyuki、Sudo Yuka、Miura Yuri、Tsumoto Hiroki、Nakagawa Yoshimi、Shimano Hitoshi、Higami Yoshikazu
    • Journal Title

      FEBS Lett

      Volume: 591 Pages: 4067-4073

    • DOI

      10.1002/1873-3468.12914

    • NAID

      120007134579

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry2017

    • Author(s)
      Sawada Yoshikazu、Izumida Yoshihiko、Takeuchi Yoshinori、Aita Yuichi、Wada Nobuhiro、Li EnXu、Murayama Yuki、Piao Xianying、Shikama Akito、Masuda Yukari、Nishi-Tatsumi Makiko、Kubota Midori、Sekiya Motohiro、Matsuzaka Takashi、Nakagawa Yoshimi、Shimano Hitoshi、Yahagi Naoya
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Pages: 40-45

    • DOI

      10.1016/j.bbrc.2017.09.081

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 12. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.2017

    • Author(s)
      Shimano H, Sato R.
    • Journal Title

      Nat Rev Endocrinol.

      Volume: 13(12) Pages: 710-730

    • DOI

      10.1038/nrendo.2017.91

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elovl6 Deficiency Improves Glycemic Control in Diabetic db / db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity2017

    • Author(s)
      Zhao Hui、Matsuzaka Takashi、Nakano Yuta、Motomura Kaori、Tang Nie、Yokoo Tomotaka、Okajima Yuka、Han Song-iee、Takeuchi Yoshinori、Aita Yuichi、Iwasaki Hitoshi、Yatoh Shigeru、Suzuki Hiroaki、Sekiya Motohiro、Yahagi Naoya、Nakagawa Yoshimi、Sone Hirohito、Yamada Nobuhiro、Shimano Hitoshi
    • Journal Title

      Diabetes.

      Volume: 66 Pages: 1833-1846

    • DOI

      10.2337/db16-1277

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] セラミドの脂肪酸鎖長によるインスリン感受性制御機構と血中脂質2020

    • Author(s)
      松坂 賢、島野 仁
    • Organizer
      第62回 日本脂質生化学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 動脈硬化とNAFLD共通病態を脂質代謝からみつめる2020

    • Author(s)
      島野 仁
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] セラミドの脂肪酸分子種によるプロテインホスファターゼ2Aの活性制御機構:脂肪酸伸長酵素Elovl6の重要性とインスリン感受性における意義2020

    • Author(s)
      松坂 賢、島野 仁
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 学際研究で切り拓く脂質とアミノ酸のメタボダイナミズム 脂肪酸の量と質とセンシングの視点からみた脂質多様性とメタボダイナミズム2020

    • Author(s)
      島野 仁、松坂 賢、関谷元博、宮本崇史
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 学際研究で切り拓く脂質とアミノ酸のメタボダイナミズム 質量分析を用いた組織・細胞の脂質メタボロミクスとトランスレーショナル応用2020

    • Author(s)
      林 昭夫、松坂 賢、島野 仁
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] コレステロールとトリグリセリド2020 revisit2020

    • Author(s)
      島野 仁
    • Organizer
      第35回日本糖尿病合併症学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 転写因子SREBP-1aによる腸管内脂質制御が腸管内部構造に与える影響の検討2020

    • Author(s)
      荒木雅弥、中川嘉、韓松伊、水之江雄平、王農雨、松坂賢、関谷元博、矢作直也、島野 仁
    • Organizer
      第74回日本栄養・食糧学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Causal SNV探索を通じたApoA1遺伝子の新たな発現調節機構の解明2020

    • Author(s)
      曾田雄一、矢作直也、武内謙憲、何敏熙、Zahra MS、呼延宜人、村山友樹、志鎌明人、升田紫、泉田欣彦、関谷元博、中川嘉、松坂賢、川上康、島野 仁
    • Organizer
      第52回日本動脈硬化学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝臓特異的Elovl6欠損マウスの肝臓ではC18-ceramideが減少することによりインスリン感受性が亢進する2020

    • Author(s)
      松坂賢、久芳素子、小安さおり、本村香織、大野博、Sharma R、武内謙憲、矢作直也、宮本崇史、関谷元博、中川嘉、島野 仁
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝臓特異的Elovl6欠損マウスの肝臓ではC18-ceramideが減少することによりインスリン感受性が亢進する2020

    • Author(s)
      松坂賢、久芳素子、小安さおり、本村香織、大野博、Sharma R、武内謙憲、矢作直也、宮本崇史、関谷元博、中川嘉、島野 仁
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Elucidation of Apoa1 Gene Regulatory Mechanism Through Searching Causal Single-Nucleotide Variants2020

    • Author(s)
      Aita Y, Yahagi N, Takeuchi Y, Ho MH, Saber ZM, Huyan Y, Murayama Y, Shikama A, Masuda Y, Izumida Y, Sekiya M, Nakagawa Y, Matsuzaka T, Kawakami Y, Shimano H
    • Organizer
      American Heart Association Scientific Sessions 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MicroRNA(s) that Regulates ELOVL62020

    • Author(s)
      Nurani Istiqamah, Takashi Matsuzaka, Hitoshi Shimano
    • Organizer
      Tsukuba Global Science Week (TGSW) 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Respiratory activity in psoriatic circulating T cells predicts the efficacy of apremilast2020

    • Author(s)
      Koguchi-Yoshioka H, Watanabe R, Matsumura Y, Shimano H, Fujimoto M
    • Organizer
      Virtual Conference of the Society-for-Investigative-Dermatology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小腸切除モデルマウスを用いた小腸切除後の栄養トランスポーター関連遺伝子発現変化の検討2020

    • Author(s)
      佐々木理人、小野健太郎、堀口比奈子、白根和樹、根本悠里、田中尚、相吉翼、千葉史子、神保教広、瓜田泰久、新開統子、高安肇、中川嘉、島野 仁、増本幸二
    • Organizer
      第35回日本臨床栄養代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 小腸切除マウスの肝臓における脂質代謝関連遺伝子発現の検討2020

    • Author(s)
      小野健太郎、佐々木理人、松坂賢、島野 仁、増本幸二
    • Organizer
      第35回日本臨床栄養代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 心血管疾患のリスク病態としてのNAFLD/NASH(合同シンポジウム)2019

    • Author(s)
      島野仁
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脂質の量と質の変容がもたらす臓器病態と栄養戦略2019

    • Author(s)
      島野仁
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A novel aspect of fatty acid chain length in lipotoxicity: Lessons from Elovl6 KO mice2019

    • Author(s)
      Hitoshi Shimano
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A metabolite sensor CtBP2 integrates metabolic flux to orchestrate glucose and lipid homeostasis in liver2019

    • Author(s)
      Motohiro Sekiya, Hitoshi Shimano, Gokhan Hotamisligil
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CREB3L3欠損による動脈硬化発症の分子メカニズム2017

    • Author(s)
      中川 嘉、関谷 元博、松坂 賢、島野 仁
    • Organizer
      第32回 日本糖尿病合併症学会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 筑波大学 内分泌代謝・糖尿病内科

    • URL

      https://www.u-tsukuba-endocrinology.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 筑波大学 医学医療系 内分泌代謝・糖尿病内科

    • URL

      https://www.u-tsukuba-endocrinology.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 筑波大学 医学医療系 内分泌代謝・糖尿病代謝内科

    • URL

      http://www.u-tsukuba-endocrinology.jp/index.html

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 生細胞内論理ゲートによるオルガネラの形態操作法2019

    • Inventor(s)
      宮本崇史、松坂賢、島野仁
    • Industrial Property Rights Holder
      宮本崇史、松坂賢、島野仁
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-211266
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-07-04   Modified: 2021-12-27  

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