Control of energy metabolism by changes of the organ lipid quality through fatty acid elongase Elovl6.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• 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): NAKAGAWA Yoshimi 筑波大学, 医学医療系, 講師 (80361351) ; IIDA Koaruko お茶の水女子大学, 人間文化創成科学研究科ライフサイエンス専攻, 准教授 (50375458) ; MATSUZAKA Takashi 筑波大学, 医学医療系, 准教授 (70400679) ; ISHII Kiyoaki 筑波大学, 医学医療系, 助教 (80419150)
• Project Period (FY): 2009 – 2011
• Keywords: 脂肪酸 / エネルギー代謝 / インスリン感受性

Research Abstract

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), brain-specific Elovl6 deficient mice (BKO), and Elovl6^<-/-> bone marrow cells-transplanted LDLR^<-/-> mice, and aimed to elucidate the physiological role of Elovl6 in the liver, feeding behavior, and atherosclerosis. High sucrose diet-feeding in LKO mice caused higher insulin sensitivity than those of flox mice. BKO mice showed the change of dietary preference. Aortic atherosclerotic lesion areas were significantly smaller in Elovl6^<-/-> bone marrow cells-transplanted LDLR^<-/-> mice than in wild-type. These results suggest that inhibiting Elovl6 activity may provide a novel therapeutic approach for treating insulin resistance, diabetes, metabolic syndrome, and cardiovascular risks by circumventing obesity problems.

Research Products

• [Journal Article] TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances in sulin sensitivity in mice (2012)
  • Author(s): Iwasaki H, Naka A, Iida KT, Nakagawa Y, Matsuzaka T, Ishii KA, Kobayashi K, Takahashi A, Yatoh S, Yahagi N, Sone H, Suzuki H, Yamada N, Shimano H
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302(7) Pages: E896-902
  • Peer Reviewed
• [Journal Article] Novel qualitative aspects of tissue fatty acids related to metabolic regulation : Lessons from Elovl6 knockout (2012)
  • Author(s): Shimano H
  • Journal Title: Prog Lipid Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Macrophage Elovl6deficiency ameliorates foam cell formation and reduces atherosclerosis in low-density lipoprotein receptor-deficient mice (2011)
  • Author(s): Saito R, Matsuzaka T, Karasawa T, Sekiya M, Okada N, Igarashi M, Matsumori R, Ishii K, Nakagawa Y, Iwasaki H, Kobayashi K, Yatoh S, Takahashi A, Sone H, Suzuki H, Yahagi N, Yamada N, Shimano H
  • 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 hep atosteatosis through Kruppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice (2011)
  • Author(s): Kumadaki S, Karasawa T, Matsuzaka T, Ema M, Nakagawa Y, Nakakuki M, Saito R, Yahagi N, Iwasaki H, Sone H, Takekoshi K, Yatoh S, Kobayashi K, Takahashi A, Suzuki H, Takahashi S, Yamada N, Shimano H
  • Journal Title: J Biol Chem Volume: 286(47) Pages: 40835-46
  • Peer Reviewed
• [Journal Article] Sterol regulatory element-binding protein-1 determines plasma remnant lipoprotein sand accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice (2011)
  • Author(s): Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31(8) Pages: 1788-95
  • Peer Reviewed
• [Journal Article] Suppression of the pancreatic duodenal homeodomain transcription factor-1 (Pdx-1) promoter by sterol regulatory element-binding protein-1c (SREBP-1c) (2011)
  • Author(s): Amemiya-Kudo M, Oka J, Takeuchi Y, Okazaki H, Yamamoto T, Yahagi N, Matsuzaka K, Okazaki S, Osuga J, Yamada N, Murase T, Shimano H
  • Journal Title: J Biol Chem Volume: 286(32) Pages: 27902-14
  • Peer Reviewed
• [Presentation] A novel bile salt sequestering agent PEGylated a nd quaternized polyamine nanogel reduces VLDL and LDL cholesterol, raises HDL cholesterol, and prevents atherosclerosis in mice (2011)
  • Author(s): Haruna Shinozaki, Takashi Matsuzaka, Yukio Nagasaki, Hitoshi Shimano, et al
  • Organizer: 第34回日本分子生物学会年会
  • Year and Date: 20111214-15
• [Presentation] A novelbile salt sequestering agent_"PEGylated andquaternized polyamine nanogel reduces VLDL and LDL cholesterol, raises HDL cholesterol, and prevents atherosclerosis in mice (2011)
  • Author(s): Rie Matsumori, Takashi Matsuzaka, Yukio Nagasaki, Hitoshi Shimano, et al
  • Organizer: 第84回米国心臓協会学術集会
  • Place of Presentation: AHA Scientific Sessions2011
  • Year and Date: 2011-11-15
• [Presentation] PEGylatedand quaternized polyamine nanogel a novelbile salt sequestering agent, ameliorates dyslipidmia through reduction of VLDL and LDL cholesterol, and induction of HDL cholesterol (2011)
  • Author(s): Rie Matsumori, Takashi Matsuzaka, Yukio Nagasaki, Hitoshi Shimano, et al
  • Organizer: 第43 回日本動脈硬化学会学術集会
  • Year and Date: 2011-07-16
• [Presentation] 動脈硬化戦略における脂質管理の新しい視点:臓器脂質の量的制御と質的制御 (2011)
  • Author(s): 島野仁
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-20
• [Presentation] 飢餓応答肝臓特異的転写因子CREBHの糖脂質代謝制御 (2011)
  • Author(s): 島野仁
  • Organizer: 第84回日本内分泌学会年次学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-21
• [Remarks]
  • URL: http://www.u-tsukuba-endocrinology.jp/