Elucidation of the regulatory mechanism of fatty acid composition in the cell and its role in brain function and mental disease

• Project/Area Number: 24680072
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUZAKA Takashi 筑波大学, 医学医療系, 准教授 (70400679)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000); Fiscal Year 2014: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2012: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 脂肪酸 / 脳 / ニューロン / アストロサイト / 海馬

Outline of Final Research Achievements

We analyzed the role of fatty acid elongase Elovl6 in brain by using Elovl6 deficient mice and brain-specific Elovl6 deficient mice. Elovl6 deficiency in brain caused decreased the relative content of stearate (C18:0) and increased the relative content of palmitate (C16:0) compared to control. The weight of the brain was significantly heavier in Elovl6 deficient mice than in wild- type mice. Mutant hippocampus exhibited decreased neural precursors and spine density. Memory impairment, enhanced anxiety and decreased motivation were observed in Elovl6 deficient mice. Moreover, Elovl6 deficiency increased proliferation and differentiation of astrocyte and neuron in primary hippocampal culture cells. Thus, Elovl6 is crucial for the development and function of the central nervous system.

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
• [Journal Article] Elovl6 promotes nonalcoholic steatohepatitis (2012)
  • Author(s): Takashi Matsuzaka, et al
  • Journal Title: Hepatology Volume: 56 Issue: 6 Pages: 2199-2208
  • DOI: 10.1002/hep.25932
  • Peer Reviewed
• [Presentation] 高次脳機能における脂肪酸伸長酵素Elovl6の役割 (2014)
  • Author(s): 大野博、松坂賢、吉田恵里子、伏見友希、所司慶太、島野仁
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-27
• [Presentation] 脳神経系の形成と発達における脂肪酸伸長酵素Elovl6の役割 (2014)
  • Author(s): 吉田恵里子、松坂賢、大野博、伏見友希、所司慶太、島野仁
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-27
• [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
• [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
• [Presentation] Elovl6 promotes nonalcoholic steatohepatitis in mice and humans. (2012)
  • Author(s): Takashi Matsuzaka. 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
• [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、齋藤亮、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55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
• [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/
• [Remarks]
  • URL: http://www.u-tsukuba-endocrinology.jp/