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

• Project/Area Number: 24390230
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University 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: ¥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.

Research Products

• [Journal Article] Ligand-activated PPARα-dependent DNA demethylation regulates the fatty acid β-oxidation genes in the postnatal liver. (2015)
  • 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) Pages: 775-784
  • DOI: 10.2337/db14-0158
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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) Pages: 4706-19
  • DOI: 10.1210/en.2014-1113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High Risk of Failing Eradication of Helicobacter Pylori in Patients with Diabetes: A Meta-analysis (2014)
  • Author(s): Horikawa C, Kodama S, Fujihara K, Hirasawa R, Yachi Y, Suzuki A, Hanyu O, Shimano H, Sone H
  • Journal Title: Diabetes research and clinical practice Volume: 106 Pages: 81-7
  • DOI: 10.1016/j.diabres.2014.07.009
  • 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
  • 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) Pages: 318-23
  • DOI: 10.1016/j.bbrc.2014.05.113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of Helicobacter Pylori Infection with Glycemic Control in Patients with Diabetes: A Meta-analysis (2014)
  • Author(s): Horikawa C, Kodama S, Fujihara K, Yachi Y, Tanaka S, Suzuki A, Hanyu O, Shimano H, Sone H
  • Journal Title: Journal of Diabetes Research Volume: - Pages: 250620-250620
  • DOI: 10.1155/2014/250620
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis (2014)
  • 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: Nature Comminications Volume: 5 Pages: 1-14
  • DOI: 10.1038/ncomms4147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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) Pages: 1791-1802
  • DOI: 10.1002/hep.26951
  • 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: Nature Commun Volume: 4:2883 Pages: 1-12
  • DOI: 10.1038/ncomms3883
  • NAID: 120005349007
  • 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 diet (2013)
  • 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
  • DOI: 10.1152/ajpendo.00419.2013
  • Peer Reviewed
• [Journal Article] Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice (2013)
  • Author(s): Sunaga Hiroaki, Kurabayashi Masahiko
  • Journal Title: Nat Commun. Volume: vol.4 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: Nature Communications Volume: 4 Pages: 2316-2316
  • DOI: 10.1038/ncomms3316
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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: Biochem Biophys Res Commun Volume: 430 Pages: 664-669
  • DOI: 10.1016/j.bbrc.2012.11.094
  • Peer Reviewed / Open Access
• [Journal Article] Elovl6 promotes nonalcoholic steatohepatitis (2012)
  • Author(s): Takashi Matsuzaka, et al
  • Journal Title: Hepatology. Volume: 56 Pages: 2199-208
  • DOI: 10.1002/hep.25932
  • 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 Pages: 931-6
  • DOI: 10.1016/j.bbrc.2012.03.110
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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] 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
• [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
• [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
• [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
• [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
  • URL: http://www.u-tsukuba-endocrinology.jp/index.html
• [Remarks] 筑波大学 内分泌代謝・糖尿病内科
  • URL: http://www.u-tsukuba-endocrinology.jp/
• [Remarks]
  • URL: http://www.u-tsukuba-endocrinology.jp/