Fatty acid elongase ELOVL1: function and diseases

• Project/Area Number: 24590073
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: SASSA Takayuki 北海道大学, 薬学研究科(研究院), 講師 (20342793)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 極長鎖脂肪酸 / スフィンゴ脂質 / 皮膚バリア / セラミド / 脂質

Outline of Final Research Achievements

To elucidate the function of saturated and monounsaturated very long-chain fatty acids, we made mice lacking Elovl1, the gene responsible for very long-chain-fatty acid production. Elovl1 knockout mice exhibited impaired epidermal permeability barrier and died neonatally. In the epidermis of Elovl1 knockout mice, the level of acylceramides, the lipids important for epidermal permeability barrier, was severely reduced, demonstrating that Elovl1 is one of the enzyme essential for the synthesis of acylceramides.

Research Products

• [Journal Article] Metabolism of very long-chain fatty acids : genes and pathophysiology (2014)
  • Author(s): Sassa T, Kihara A
  • Journal Title: Biomol. Ther Volume: 22 Issue: 2 Pages: 83-92
  • DOI: 10.4062/biomolther.2014.017
  • Peer Reviewed / Open Access
• [Journal Article] Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid (2014)
  • Author(s): Sassa T, Wakashima T, Ohno Y, Kihara A
  • Journal Title: Journal of lipid research Volume: 55 Issue: 3 Pages: 524-530
  • DOI: 10.1194/jlr.m044586
  • NAID: 120005457018
  • Peer Reviewed
• [Journal Article] Impaired epidermal permeability barrier in mice lacking the Elovl1 gene responsible for very long-chain fatty acid production. (2013)
  • Author(s): Sassa T, Ohno Y, Suzuki S, Nomura T, Nishioka C, Kashiwagi T, Hirayama T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A.
  • Journal Title: Mol Cell Biol Volume: 33 Issue: 14 Pages: 2787-2796
  • DOI: 10.1128/mcb.00192-13
  • Peer Reviewed
• [Journal Article] Cooperative synthesis of ultra long-chain fatty acid and ceramide during keratinocyte differentiation. (2013)
  • Author(s): Mizutani Y, Sun, H Ohno Y, Sassa T, Wakashima T, Obara M, Yuyama K, Kihara A and Igarashi Y.
  • Journal Title: PLoS One Volume: 8
  • NAID: 120005322424
  • Peer Reviewed
• [Journal Article] Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile (2013)
  • Author(s): Abe K, Ohno Y, Sassa T, Taguchi R, Çali şkan, M, Ober C, Kihara A
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 51 Pages: 36741-36749
  • DOI: 10.1074/jbc.m113.493221
  • NAID: 120005385316
  • Peer Reviewed
• [Presentation] Aldh3a2 knockout mice as a potential model for Sjogren-Larsson syndrome. (2015)
  • Author(s): Sassa T, Kanetake T, Naganuma T, Takagi S, Kitamura T and Kihara A
  • Organizer: 6th International Conference on Phospholipase A2 and Lipid Mediators (PLM2015)
  • Place of Presentation: Keio Plaza Hotel, Shinjuku, Tokyo
  • Year and Date: 2015-02-15
• [Presentation] C24極長鎖脂肪酸の生理機能と病態への関与 (2014)
  • Author(s): 佐々貴之
  • Organizer: 第7回セラミド研究会学術集会
  • Place of Presentation: 東京 ユビキタス協創広場 CANVAS，東京
  • Year and Date: 2014-10-31
  • Invited
• [Presentation] シェーグレン・ラルソン症候群原因遺伝子Aldh3a2 KOマウスを用いた脳における生化学的解析 (2014)
  • Author(s): 金武司, 佐々貴之, 高木秀侑, 永沼達郎, 木原章雄
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会議場，京都
  • Year and Date: 2014-10-16
• [Presentation] シェーグレン・ラルソン症候群原因遺伝子ALDH3A2の表皮における機能解析 (2014)
  • Author(s): 高木秀侑, 永沼達郎, 金武司, 北村拓也, 佐々貴之, 木原章雄
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会議場，京都
  • Year and Date: 2014-10-16
• [Presentation] シェーグレン・ラルソン症候群原因遺伝子Aldh3a2の欠損はマウスケラチノサイトにおいて細胞増殖の亢進とアシルセラミド量の低下を引き起こす (2014)
  • Author(s): 永沼達郎, 高木秀侑, 金武司, 北村拓也, 佐々貴之, 木原章雄
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会議場，京都
  • Year and Date: 2014-10-16
• [Presentation] シェーグレン・ラルソン症候群における皮膚魚鱗癬発症メカニズムの解析 (2014)
  • Author(s): 永沼達郎, 高木秀侑, 金武司, 北村拓也, 佐々貴之, 木原章雄
  • Organizer: 日本生化学会北海道支部第51回支部例会
  • Place of Presentation: 北海道大学百年記念会館，札幌
  • Year and Date: 2014-07-18
• [Presentation] シェーグレン・ラルソン症候群原因遺伝子Aldh3a2ノックアウトマウスを用いた神経症状発症の分子機構の解析 (2014)
  • Author(s): 佐々貴之, 金武司, 高木秀侑, 永沼達郎, 木原章雄
  • Organizer: 第56回日本脂質生化学会
  • Place of Presentation: 近畿大学，大阪
  • Year and Date: 2014-06-07
• [Presentation] シェーグレン・ラルソン症候群原因遺伝子Aldh3a2の中枢神経系における機能解析 (2014)
  • Author(s): 金武司, 佐々貴之, 高木秀侑, 永沼達郎, 木原章雄
  • Organizer: 日本薬学会北海道支部141回例会
  • Place of Presentation: 札幌コンベンションセンター，札幌
  • Year and Date: 2014-05-24
• [Presentation] Mice lacking the Elovl1 gene responsible for very long-chain fatty acid production exhibit neonatal lethality due to impaired epidermal permeability barrier. (2013)
  • Author(s): Sassa T, Ohno Y, Suzuki S, Nomura T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A.
  • Organizer: FASEB Summer Research conferences (Lysophospholipid and Other Related Mediators - From Bench to Clinic)
  • Place of Presentation: Hilton Niseko Village, Niseko, Japan
• [Presentation] Loss of ELOVL1 enzyme causes lethal skin barrier disruption in mice. (2013)
  • Author(s): Suzuki S, Nomura T, Sassa T, Ohno Y, Nakamura H, Akiyama M, Kihara A and Shimizu H.
  • Organizer: 40th Annual Meeting of Society for Cutaneous Ultrastructure Research
  • Place of Presentation: Castellani Parkhotel, Sarzburg, Austria
• [Presentation] Loss of ELOVL1 enzyme depletes very long-chain fatty acids and causes lethal skin barrier disruption in mice. (2013)
  • Author(s): Suzuki S, Nomura T, Sassa T, Ohno Y, Akiyama M, Kihara A and Shimizu H.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: The Edinburgh International Conference Centre, Edinburgh, UK
• [Presentation] Functional characterization of very long-chain sphingolipids produced by ELOVL1 (2012)
  • Author(s): Takayuki Sassa and Akio Kihara
  • Organizer: Gordon Research Conference, Glycolipid and Sphingolipid Biology
  • Place of Presentation: Renaissance Tuscany Il Ciocco Resort (Italy)
• [Presentation] Fatty acid elongase Elovl1 is essential for the synthesis of ≥C26 ceramides and epidermal permeability barrier formation.
  • Author(s): Sassa T, Ohno Y, Suzuki S, Nomura T, Akiyama M, Taguchi R, Shimizu H, Itohara S and Kihara A.
  • Organizer: Gordon Research Conference (Glycolipid & Sphingolipid Biology)
  • Place of Presentation: Four Points Sheraton, Ventura, USA
• [Presentation] 極長鎖脂肪酸伸長酵素Elovl1は表皮において層特異的な制御を受け皮膚バリアに必須の役割を果たす.
  • Author(s): 佐々貴之, 大野祐介, 鈴木翔多朗, 乃村俊史, 秋山真志, 田口良, 清水宏, 糸原重美, 木原章雄.
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜，横浜
• [Presentation] ELOVL1の欠損は致死的な皮膚バリア障害を引き起こす.
  • Author(s): 鈴木翔多朗, 乃村俊史, 佐々貴之, 大野祐介, 中村秀樹, 秋山真志, 木原章雄, 清水宏.
  • Organizer: 第40回皮膚かたち研究学会学術大会
  • Place of Presentation: 石垣記念ホール，東京
• [Presentation] 常染色体劣性遺伝精神遅滞に見られるTER P182L変異体の生化学的解析.
  • Author(s): 安部健介, 大野祐介, 佐々貴之, 木原章雄.
  • Organizer: 第55回日本脂質生化学会
  • Place of Presentation: 松島大観荘，仙台
• [Presentation] 家族性精神遅滞に見られるTER P182L変異体の生化学的解析.
  • Author(s): 安部健介, 大野祐介, 佐々貴之, 木原章雄.
  • Organizer: 日本薬学会北海道支部140回例会
  • Place of Presentation: 札幌コンベンションセンター，札幌
• [Remarks] 北海道大学 大学院薬学研究院 生化学研究室
  • URL: http://www.pharm.hokudai.ac.jp/seika/index.html
• [Remarks] 北海道大学 薬学研究院 生化学研究室
  • URL: http://www.pharm.hokudai.ac.jp/seika/index.html
• [Remarks] 北海道大学 大学院薬学研究院 創薬科学部門 生体機能科学分野 生化学研究室
  • URL: http://www.pharm.hokudai.ac.jp/seika/index.html