Elucidation of the physiological role of fatty acid elongase Elovl6 in liver and development of new strategy for the treatment of metabolic disease

2011 Fiscal Year Final Research Report

• Project/Area Number: 21689025
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• 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)
• 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 fatty acids with 12, 14, and 16 carbons. In this research, I generated liver-specific Elovl6 deficient mice (LKO), and aimed to elucidate the physiological role of Elovl6 in the liver and identify the lipid factor which control energy metabolismand insulin sensitivity. LKO mice reduce stearate and oleate levels, and increases palmitate and palmitoleate levels in the liver. In contrast to Elovl6^<-/->. mice, LKO mice were not protected against HFHS diet. However, high sucrose diet-feeding in LKO mice caused higher insulin sensitivity than those of flox mice. These results suggest that products of the Elovl6 reaction through de novo lipogenesis regulates hepatic insulin sensitivity, but Elovl6 inhibition in extrahepatic tissue is required to protect mice from HFHS-induced insulin resistance.

Research Products

• [Journal Article] TFE3 reg ulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin 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] Macrophage Elovl6 deficiency 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: ArteriosclerThromb Vasc Biol Volume: 31(9) Pages: 1973-9
  • Peer Reviewed
• [Journal Article] In hibition of ubiquitin ligase F-box and WD re peat domain-containing 7α (Fbw7α) causes he patosteatosis 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 lipoproteins and 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
• [Presentation] A novel bile salt sequestering agent PEGylated and 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 novel bile salt sequestering agent_PEGylated and quaternized polyamine nanogel reduces VLDLand 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(AHA Scientific Sessions 2011)
  • Year and Date: 2011-11-15
• [Presentation] PEGylatedand quaternized polyamine nanogel a novel bile 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
• [Remarks]
  • URL: http://www.u-tsukuba-endocrinology.jp/