Role of fatty acid elongase Elovl6 in the sucrose preference formation

• Project/Area Number: 23659464
• 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): YATOH Shigeru 筑波大学, 医学医療系, 講師 (50451703)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脂肪酸 / 嗜好性 / 糖尿病

Research Abstract

In this study, we investigated the effects of Elovl6 deletion in leptin receptor-deficient db/db mice, a model of type 2 diabetes. We analyzed the body weights, serum glucose, insulin and HbA1c levels of db+/m, db/db, and db/db-Elovl6KO mice. We also performed immunohistochemical staining and quantitative RT-PCR analysis of islet.Although the obesity of db/db-Elovl6KO mice was similar to db/db mice, development of hyperglycemia and glucose intolerance was dramatically improved. Histological examination indicated that Elovl6 deletion was associated with increased islet mass in db/db mice, and this correlated with serum hyperinsulinemia and glucose-responsive insulin secretion. The expression of several inflammatory genes such as TNF-α and MCP-1 were reduced, and the expression of genes related to β cell function such as PDX-1 and insulin were increased in islets from db/db-Elovl6KO mice compared with db/dbmice. These results suggest that Elovl6 is an important factor on both beta-cell mass and function in T2D. Elovl6 inhibition can be a novel therapeutic target for T2D.

Research Products

• [Journal Article] TFE3 inhibits myoblast differentiation inC2C12 cells via down-regulating geneexpression of myogenin (2013)
  • Author(s): Naka A, Iida KT, Nakagawa Y, IwasakiH, Takeuchi Y, Satoh A, Matsuzaka T, IshiiKA, Kobayashi K, Yatoh S, Shimada M, YahagiN, Suzuki H, Sone H, Yamada N, Shimano H
  • Journal Title: Biochem BiophysRes Commun Volume: 430 Pages: 664-669
  • Peer Reviewed
• [Journal Article] Elovl6 promotes nonalcoholic steatohepatitis. (2012)
  • Author(s): Matsuzaka T, Atsumi A, Matsumori R, Nie T, Shinozaki H, Suzuki-Kemuriyama N, Kuba M, Nakagawa Y, Ishii K, Shimada M, Kobayashi K, Yatoh S, Takahashi A,Takekoshi K, Sone H, Yahagi N, Suzuki H, Murata S, Nakamuta M, Yamada N, Shimano H
  • Journal Title: Hepatology. Volume: 56 Pages: 2199-2208
  • Peer Reviewed
• [Journal Article] Dicer hasa crucial role in the early stage ofadipocyte differentiation, but not inlipid 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: BiochemBiophys Res Commun Volume: 420 Pages: 931-936
  • Peer Reviewed
• [Journal Article] TFE3regulates muscle metabolic geneexpression (2012)
  • Author(s): Iwasaki H, Naka A, Iida KT, NakagawaY, Matsuzaka T, Ishii KA, Kobayashi K,Takahashi A, Yatoh S, Yahagi N, Sone H,Suzuki H, Yamada N, Shimano H.
  • Journal Title: increases glycogen stores,and enhances insulin sensitivity in mice Volume: 302
  • Peer Reviewed
• [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
• [Journal Article] Macrophage Elovl6 deficiency ameliorates foam cell formation and reduces atherosclerosis in low-density lipoprotein receptor-deficient mice. (2011)
  • Author(s): Saito R, Matsuzaka T, Yamada N, Shimano H, et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 31(9) Pages: 1973-9
  • Peer Reviewed
• [Journal Article] Inhibition of ubiquitin ligase F-box and WD repeat domain-containing 7α (Fbw7α) causes hepatosteatosis through Krüppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice. (2011)
  • Author(s): Kumadaki S, Matsuzaka T, Yamada N, Shimano H, et al.
  • Journal Title: J Biol Chem. Volume: 286(47) Pages: 40835-46
  • NAID: 120007137356
  • Peer Reviewed
• [Presentation] Deletion of Elovl6 protects against thefailure of pancreatic beta-cell mass andfunction in db/db mice (2012)
  • Author(s): Yuta Nakano, Takashi Matsuzaka, NieTang, Marii Suzuki, Noriko Suzuki-Kemuriyama, Motoko Kuba, KeitaShoshi, Tomotaka Yokoo, Yoshimi Nakagawa,Kiyoaki Ishii, Masako Shimada, HitoshiIwasaki, Kazuto Kobayashi, Shigeru Yatoh,Akimitsu Takahashi, Naoya Yahagi, Hi
  • 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、福岡
  • Year and Date: 2012-12-11
• [Presentation] Elovl6 promotesnonalcoholic steatohepatitis in mice andhumans (2012)
  • Author(s): Takashi Matsuzaka, Tang Nie, NorikoSuzuki-Kemuriyama, Motoko Kuba, YoshimiNakagawa, Kiyoaki Ishii, Masako Shimada,Kazuto Kobayashi, Shigeru Yatoh, AkimitsuTakahashi, Hirohito Sone, Naoya Yahagi,Hiroaki Suzuki, Makoto Nakamuta, NobuhiroYamada, Hitoshi Shim
  • Organizer: 9th IDF-WPR Congress and 4th AASDScientific Meeting
  • Place of Presentation: 国立京都国際会館, 京都
  • 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、高橋 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、横浜
  • Year and Date: 2012-05-19
• [Presentation] Deletion of Elovl6 protects against the failure of pancreatic beta-cell mass and function in db/db mice.
  • Author(s): Yuta Nakano
  • 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
• [Presentation] Elovl6 promotes nonalcoholic steatohepatitis in mice and humans.
  • Author(s): Matsuzaka T
  • Organizer: 9th IDF-WPR Congress and 4th AASD Scientific Meeting.
  • Place of Presentation: 国立京都国際会館
• [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
  • Author(s): 松坂 賢
  • 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
• [Remarks]
  • URL: http://www.u-tsukuba-endocrinology.jp/
• [Remarks] 筑波大学 内分泌代謝・糖尿病内科
  • URL: http://www.u-tsukuba-endocrinology.jp/