Elucidation of the inflammasome regulatory mechanism by fatty acid elongase Elovl6

• Project/Area Number: 25670430
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUZAKA Takashi 筑波大学, 医学医療系, 准教授 (70400679)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Akimitsu 筑波大学, 医学医療系, 准教授 (70344893)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); 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: 脂肪酸 / 炎症 / インフラマソーム / 肝細胞 / マクロファージ

Outline of Final Research Achievements

We analyzed the role of fatty acid elongase Elovl6 in the regulation of NLRP3 inflammasome. Saturated fatty acid palmitate-induced NLRP3 inflammasome activation was suppressed in hepatocytes and macrophages of Elovl6KO mice as compared with those of wild-type mice. Moreover, we observed that one of the regulatory factors of NLRP3 inflammasome was suppressed in hepatocytes and macrophages of Elovl6KO mice. Our findings suggest that inhibition of Elovl6 could be a new therapeutic approach for ameliorating metabolic inflammation through suppression of NLRP3 inflammasome.

Research Products

• [Journal Article] Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes (2014)
  • 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
  • Peer Reviewed
• [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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New liver-β-cell axis that controls insulin secretory capacity. (2014)
  • Author(s): Matsuzaka T, Shimano H.
  • Journal Title: J Diabetes Investig. Volume: 5(3) Issue: 3 Pages: 276-7
  • DOI: 10.1111/jdi.12199
  • Peer Reviewed
• [Journal Article] Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice (2013)
  • Author(s): Sunaga Hiroaki, Kurabayashi Masahiko
  • Journal Title: Nature Communications Volume: vol.4 Issue: 1 Pages: 2563-2563
  • DOI: 10.1038/ncomms3563
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis. (2013)
  • Author(s): Fujimoto Y, Nakagawa Y, Satoh A, Okuda K, Shingyouchi A, Naka A, Matsuzaka T, Iwasaki H, Kobayashi K, Yahagi N, Shimada M, Yatoh S, Suzuki H, Yogosawa S, Izumi T, Sone H, Urayama O, Yamada N, Shimano H
  • Journal Title: Endocrinology Volume: 154 Issue: 10 Pages: 3577-88
  • DOI: 10.1210/en.2013-1203
  • Peer Reviewed / Open Access
• [Presentation] 脂肪酸伸長酵素Elovl6の欠損はdb/dbマウスの2型糖尿病の発症・進展を抑制する (2014)
  • Author(s): 松坂賢、中野雄太 、趙会、唐寧 、鈴木真璃衣、中川嘉 、嶋田昌子、武内謙憲、岩崎仁、小林和人 、矢藤繁 、高橋昭光 、矢作直也 、鈴木浩明、山田信博 、島野仁
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: フェニックスシーガイアリゾート コンベンションセンター
  • Year and Date: 2014-10-25
• [Presentation] Deletion of Elovl6 ameliorates hyperglycemia in db/db mice (2014)
  • Author(s): Takashi Matsuzaka, Yuta Nakano, Zhao Hui, Marii Suzuki, Tang Nie, Yoshimi Nakagawa, Naoya Yahagi, Nobuhiro Yamada, Hitoshi Shimano
  • Organizer: 9th Metabolic Syndrome,Type 2 Diabetes and Atherosclerosis Congress
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2014-09-13
• [Presentation] 脂肪酸伸長酵素Elovl6による脂肪酸組成制御と生活習慣病 (2014)
  • Author(s): 松坂 賢、島野 仁
  • Organizer: 日本内分泌学会 第32回内分泌代謝学サマーセミナー
  • Place of Presentation: 富士レークホテル
  • Year and Date: 2014-07-10 – 2014-07-12
  • Invited
• [Presentation] 脂肪酸伸長酵素Elovl6の欠損はdb/dbマウスの糖尿病の発症・進展を抑制する (2014)
  • Author(s): 松坂賢、中野雄太、趙会、唐寧、鈴木真璃衣、中川嘉、嶋田昌子、武内謙憲、岩崎仁、小林和人、高橋昭光、矢藤繁、矢作直也、鈴木浩明、山田信博、島野仁
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22
• [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）
• [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）
• [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）
• [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）
• [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）
• [Remarks] 筑波大学 内分泌代謝・糖尿病内科
  • URL: http://www.u-tsukuba-endocrinology.jp/
• [Remarks] 松坂研究室
  • URL: http://matsuzakalab-tsukuba.org/
• [Remarks] 筑波大学 内分泌代謝・糖尿病内科
  • URL: http://www.u-tsukuba-endocrinology.jp/
• [Remarks] 松坂研究室
  • URL: http://matsuzakalab-tsukuba.org/