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Study for tissue specific change of lipid quality and metabolism by fatty acid elongase Elovl6

Research Project

Project/Area Number 24390230
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Metabolomics
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHIMANO Hitoshi  筑波大学, 医学医療系, 教授 (20251241)

Co-Investigator(Kenkyū-buntansha) TAKASHI Matsuzaka  筑波大学, 医学医療系, 准教授 (70400679)
YOSHIMI Nakagawa  筑波大学, 医学医療系, 准教授 (80361351)
NAOYA Yahagi  筑波大学, 医学医療系, 准教授 (60420246)
石井 清朗  筑波大学, 医学医療系, 助教 (80419150)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords脂肪酸 / インスリン感受性 / 精神神経疾患 / インスリン抵抗性 / インスリン分泌 / 炎症 / 糖尿病 / 肝臓 / 膵β細胞 / 脳
Outline of Final Research Achievements

Elovl6 is a microsomal enzyme involved in the elongation of saturated and monounsaturated FAs with 12, 14, and 16 carbons. In this research, we generated liver-specific Elovl6 deficient mice (LKO) and brain-specific Elovl6 deficient mice (BKO), and aimed to elucidate the role of Elovl6 in the liver and brain. High carbohydrate diet-feeding in LKO mice caused lower blood glucose and higher insulin sensitivity than those of flox mice. BKO mice showed increased brain weight, decreased neural precursors, decreased spine density, and memory impairment. These results suggest that undarstanding of tissue or cell specific role of Elovl6 may provide a novel therapeutic approach for treating lifestyle-related disease and mental and neurological disorders based on control of fatty acid composition.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (34 results)

All 2015 2014 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (16 results) (of which Invited: 5 results) Remarks (3 results)

  • [Journal Article] Ligand-activated PPARα-dependent DNA demethylation regulates the fatty acid β-oxidation genes in the postnatal liver.2014

    • Author(s)
      Ehara T, Kamei Y, Yuan X, Takahashi M, Kanai S, Tamura E, Tsujimoto K, Tamiya T, Nakagawa Y, Shimano H, Takai-Igarashi T, Hatada I, Suganami T, Hashimoto K, Ogawa Y.
    • Journal Title

      Diabetes.

      Volume: 64(3) Issue: 3 Pages: 775-84

    • DOI

      10.2337/db14-0158

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes2014

    • Author(s)
      Yoshimi Nakagawa,* Aoi Satoh,* Sachiko Yabe,* Mika Furusawa, Naoko Tokushige, Hitomi Tezuka, Motoki Mikami, Wakiko Iwata, Akiko Shingyouchi, Takashi Matsuzaka, Shiori Kiwata, Yuri Fujimoto, Yasushi Kawakami, Osamu Urayama, Nobuhiro Yamada, and Hitoshi Shimano et. al
    • Journal Title

      Endocrinology

      Volume: 155(12) Issue: 12 Pages: 4706-4719

    • DOI

      10.1210/en.2014-1113

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High Risk of Failing Eradication of Helicobacter Pylori in Patients with Diabetes: A Meta-analysis2014

    • Author(s)
      Horikawa C, Kodama S, Fujihara K, Hirasawa R, Yachi Y, Suzuki A, Hanyu O, Shimano H, Sone H
    • Journal Title

      Diabet Res Clin Prac

      Volume: 106 Issue: 1 Pages: 81-7

    • DOI

      10.1016/j.diabres.2014.07.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Utility of the triglyceride level for predicting incident diabetes mellitus according to the fasting status and body mass index category: the Ibaraki Prefectural Health Study.2014

    • Author(s)
      Fujihara K, Sugawara A, Heianza Y, Sairenchi T, Irie F, Iso H, Doi M, Shimano H, Watanabe H, Sone H, Ota H.
    • Journal Title

      J Atheroscler Thromb.

      Volume: 21(11) Pages: 1152-69

    • NAID

      130004704369

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion.2014

    • Author(s)
      Tang N, Matsuzaka T, Suzuki M, Nakano Y, Zao H, Yokoo T, Suzuki-Kemuriyama N, Kuba M, Okajima Y, Takeuchi Y, Kobayashi K, Iwasaki H, Yatoh S, Takahashi A, Suzuki H, Sone H, Shimada M, Nakagawa Y, Yahagi N, Yamada N, Shimano H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 450(1) Issue: 1 Pages: 318-23

    • DOI

      10.1016/j.bbrc.2014.05.113

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Association of Helicobacter Pylori Infection with Glycemic Control in Patients with Diabetes: A Meta-analysis2014

    • Author(s)
      Horikawa C, Kodama S, Fujihara K, Yachi Y, Tanaka S, Suzuki A, Hanyu O, Shimano H, Sone H
    • Journal Title

      J Diab Res

      Volume: - Pages: 250620-250620

    • DOI

      10.1155/2014/250620

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis2014

    • Author(s)
      Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 3147-3147

    • DOI

      10.1038/ncomms4147

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen receptor/Liver X receptor pathway in mice.2014

    • Author(s)
      Han SI, Komatsu Y, Murayama A, Steffensen KR, Nakagawa Y, Nakajima Y, Suzuki M, Oie S, Parini P, Vedin LL, Kishimoto H, Shimano H, Gustafsson JÅ, Yanagisawa J.
    • Journal Title

      Hepatology

      Volume: 59(5) Issue: 5 Pages: 1791-1802

    • DOI

      10.1002/hep.26951

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.2013

    • Author(s)
      Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
    • Journal Title

      Nat Commun.

      Volume: 4:2883 Issue: 1 Pages: 2883-2883

    • DOI

      10.1038/ncomms3883

    • NAID

      120005349007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP1c Tg mice fed high-fat and high-fructose diet2013

    • Author(s)
      Wada T, Miyashita Y, Sasaki M, Aruga Y, Nakamura Y, Ishii Y, Sasahara M, Kanasaki K, Kitada M, Koya D, Shimano H, Tsuneki H, Sasaoka
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 305 Issue: 11 Pages: E1415-E1425

    • DOI

      10.1152/ajpendo.00419.2013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice2013

    • Author(s)
      Sunaga Hiroaki, Kurabayashi Masahiko
    • Journal Title

      Nature Communications

      Volume: vol.4 Issue: 1 Pages: 2563-2563

    • DOI

      10.1038/ncomms3563

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization.2013

    • Author(s)
      Izumida Y, Yahagi N, Takeuchi Y, Nishi M, Shikama A, Takarada A, Masuda Y, Kubota M, Matsuzaka T, Nakagawa Y, Iizuka Y, Itaka K, Kataoka K, Shioda S, Niijima A, Yamada T, Katagiri H, Nagai R, Yamada N, Kadowaki T, Shimano H
    • Journal Title

      Nat Commun.

      Volume: 4 Issue: 1 Pages: 2316-2316

    • DOI

      10.1038/ncomms3316

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TFE3 inhibits myoblast diffrentiation in C2C12 cells via down-regulating gene expression of myogenin.2013

    • Author(s)
      Naka A, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 430 Issue: 2 Pages: 664-669

    • DOI

      10.1016/j.bbrc.2012.11.094

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elovl6 promotes nonalcoholic steatohepatitis2012

    • Author(s)
      Takashi Matsuzaka, et al
    • Journal Title

      Hepatology

      Volume: 56 Issue: 6 Pages: 2199-2208

    • DOI

      10.1002/hep.25932

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dicer has a crucial role in the early stage of adipocyte differentiation, but not in lipid synthesis, in 3T3-L1 cells.2012

    • Author(s)
      Fujimoto Y, Nakagawa Y, Shingyouchi A, Tokushige N, Nakanishi N, Satoh A, Matsuzaka T, Ishii KA, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yahagi N, Urayama O, Yamada N, Shimano H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420 Issue: 4 Pages: 931-6

    • DOI

      10.1016/j.bbrc.2012.03.110

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脂質酸の量と質からみた脂肪毒性病態と糖尿病2015

    • Author(s)
      島野仁
    • Organizer
      第49回糖尿病学の進歩
    • Place of Presentation
      ホテルグランヴィア岡山
    • Year and Date
      2015-02-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脂質の質に視点をおいた生活習慣病治療戦略2015

    • Author(s)
      島野仁
    • Organizer
      つくば医工連携フォーラム2015~食と農から医療・健康を科学する
    • Place of Presentation
      農林水産技術会議筑波事務所内 農林ホール
    • Year and Date
      2015-01-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 新たな脂質の質的指標:脂肪酸鎖長を介した生体制御と病態の臓器的展開、Elovl6KOマウス解析を通じて2014

    • Author(s)
      島野仁
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A new aspect of organ lipids in metabolic diseases, lessons from Elovl6.2014

    • Author(s)
      Hitosh Shimano
    • Organizer
      Homeodynamics in Clocks, Sleep and Metabolism ―Tokyo Tanslational therapeutics meeting
    • Place of Presentation
      Ito Hall, Ito Internatonal Research Center, The University of Tokyo
    • Year and Date
      2014-09-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] New Aspect of Organ Lipids in Metablic Diseases and Atherosclerosis from Quantity to Quality: Lessons from Elovl6.2014

    • Author(s)
      Hitoshi Shimano
    • Organizer
      9th Metablic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2014-09-12 – 2014-09-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] アディポサイエンスからみた動脈硬化性疾患予防の展望2013

    • Author(s)
      島野仁
    • Organizer
      第13回動脈硬化教育フォーラム
    • Place of Presentation
      国立京都国際会館(招待講演)
    • Year and Date
      2013-02-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] Deletion of Elovl6 protects against the failure of pancreatic beta-cell mass and function in db/db mice.2012

    • Author(s)
      Yuta Nakano, Takashi Matsuzaka, Nie Tang, Marii Suzuki, Noriko Suzuki-Kemuriyama, Motoko Kuba, Keita Shoshi, Tomotaka Yokoo, Yoshimi Nakagawa, Kiyoaki Ishii, Masako Shimada, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano.
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Elov16 promotes nonalcoholic steatohepatitis in mice and humane.2012

    • Author(s)
      Takashi Matauzaka, Tang Nie, Noriko Suzuki-Kemuriyama, Motoko Kuba, Yoshimi Nakagawa, Kiyoaki Ishii, Masako Shimada, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Hirohito Sone, Naoya Yahagi, Hiroaki Suzuki, Makoto Nakamuta, Nobuhiro Yamada, Hitoshi Shimano.
    • Organizer
      9th IDF-WPR Congress and 4th AASD Scientific Meeting
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-11-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖尿病へのアプローチ:病態メカニズムオリエンテッドとエネルギー代謝ネットワーク的視点2012

    • Author(s)
      島野仁
    • Organizer
      第1回日本くすりと糖尿病学会学術集会
    • Place of Presentation
      星薬科大学本館メインホール-新星館(招待講演)
    • Year and Date
      2012-09-23
    • Related Report
      2012 Annual Research Report
  • [Presentation] マクロファージ泡沫化および動脈硬化における脂肪酸伸長酵素Elovl6の役割2012

    • Author(s)
      松坂賢、斎藤亮、唐澤直義、松森理恵、煙山紀子、中川嘉、石井清朗、岩崎仁、小林和人、矢藤繁、高橘昭光、曽根博仁、鈴木浩明、矢作直也、山田信博、島野仁
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2012-05-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脂質の質に視点をおいた脂質代謝疾患治療戦略2012

    • Author(s)
      島野仁
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋国際会議場(招待講演)
    • Year and Date
      2012-04-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脂肪酸伸長酵素Elovl6の欠損は高コレステロール食誘導性脂肪肝を改善する

    • Author(s)
      久芳素子、松坂賢、煙山紀子、唐ネ、大野博、中川嘉、矢藤繁、嶋田昌子、矢作直也、鈴木浩明、山田信博、島野仁
    • Organizer
      第45回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝炎における脂肪酸伸長酵素Elovl6の役割

    • Author(s)
      松坂賢、渥美綾香、唐寧、煙山紀子、久芳素子、中川嘉、嶋田昌子、小林和人、矢藤繁、高橋昭光、曽根博仁、矢作直也、鈴木浩明、中牟田誠、山田信博、島野仁
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脂肪酸伸長酵素Elovl6欠損マウスの摂食行動解析

    • Author(s)
      煙山(鈴木)紀子、松坂賢、所司慶太、加藤淳子、唐ネ、久芳素子、岩崎仁、小林和人、矢藤繁、石井清明、中川嘉、嶋田昌子、矢作直也、鈴木浩明、山田信博、島野仁
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脂肪酸伸長酵素Elovl6欠損マウスはショ糖嗜好性が亢進する

    • Author(s)
      煙山(鈴木)紀子、松坂賢、所司慶太、加藤淳子、唐ネ、久芳素子、岩崎仁、小林和人、矢藤繁、石井清明、中川嘉、嶋田昌子、矢作直也、鈴木浩明、山田信博、島野仁
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵ベータ細胞における脂肪酸伸長酵素Elovl6の役割

    • Author(s)
      唐ネ、松坂賢、鈴木真璃衣、中野雄太、煙山(鈴木)紀子、久芳素子、岩崎仁、小林和人、矢藤繁、石井清明、中川嘉、嶋田昌子、矢作直也、鈴木浩明、山田信博、島野仁
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Related Report
      2013 Annual Research Report
  • [Remarks] 筑波大学 内分泌代謝・糖尿病

    • URL

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

    • Related Report
      2014 Annual Research Report
  • [Remarks] 筑波大学 内分泌代謝・糖尿病内科

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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