Biological and pharmaceutical study on intracellular lipid droplets which are the key organelle to understand life style diseases.

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590076
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Showa University
• Principal Investigator: ITABE Hiroyuki Showa University, 薬学部, 教授 (30203079)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Katsuhiko 昭和薬科大学, 准教授 (80307066) ; KATO Rina 昭和大学, 薬学部, 助教 (30392400) ; OBAMA Takashi 昭和大学, 薬学部, 助教 (60395647)
• Project Period (FY): 2007 – 2008
• Keywords: 細胞内脂肪滴 / ADRP / 脂肪酸 / グルカゴン / Aキナーゼ

Research Abstract

生活習慣病の要因である肥満や高脂血症は、脂質代謝異常に起因する。脂質代謝の基盤として注目されている細胞内脂肪滴は、種々細胞に普遍的に存在し脂質の蓄積と利用を担う構造体である。絶食により一過的に脂肪蓄積が亢進するマウス肝で、脂肪滴局在タンパク質のADRPが顕著に誘導され、そのADRPは通常の脂肪滴や膜画分とは異なる中間比重画分に分布することを見出した。培養肝細胞HuH-7に脂肪酸を添加すると、ADRPが誘導され脂肪滴が生成するが中間比重脂肪滴は生じない。一方、グルカゴン刺激すると中間比重脂肪滴が出現した。この反応はジブチリルcAMPで再現され、Aキナーゼ阻害剤によって抑制されたことから、肝細胞内脂肪滴形成を伴う脂肪蓄積に、グルカゴン刺激によるcAMP依存性の調節機構が存在することが示された。

Research Products

• [Journal Article] Docosahexaenoic acid induces adipose differentiation-related protein through activation of retinoid X receptor in human choriocarcinoma BeWo cells (2009)
  • Author(s): Suzuk K, Takahashi K, Nishimaki-Mogami T, Kagechika H, Yamamoto M, and Itabe H.
  • Journal Title: Biol. Pharm. Bull (In press)
• [Journal Article] Transient increase in plasma oxidized LDL during the progression of atherosclerosis in apolipoprotein E knockout mice (2009)
  • Author(s): Kato R, Mori C, Kitazato K, Arata S, Obama T, Mori M, Takahashi K, Aiuchi T, Takano T, and Itabe H.
  • Journal Title: Arterioscler Thromb Vasc Biol 29(1) Pages: 33-39
• [Journal Article] Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice (2008)
  • Author(s): Shiraishi Y, Watanabe T, Suguro T, Nagashima M, Kato R, Hongo S, Itabe H, Miyazaki A, Hirano T, Adachi M.
  • Journal Title: J. Hypertens 26(10) Pages: 1955-1965
• [Journal Article] Analyses of group III secreted phospholipase A2 transgenic mice reveals potential participation of this enzyme in plasma lipoprotein modification (2008)
  • Author(s): Sato H, Kato R, Isogai Y, Saka G, Ohtsuki M, Taketomi Y, Yamamoto K, Tsutsumi K, Yamada J, Masuda S, Ishikawa Y, Ishii T, Kobayashi T, Ikeda K, Taguchi R, Hatakeyama S, Hara S, Kudo I, Itabe H, and Murakami M.
  • Journal Title: macrophage foam cell Formation, and atherosclerosis. J. Biol. Chem. 283(48) Pages: 33483-33497
• [Journal Article] Analysis of modified apolipoprotein B-100 structures formed in oxidized low-density lipoprotein using LC-MS/MS (2007)
  • Author(s): Obama T, Kato R, Masuda Y, Takahashi K, Aiuchi T, and Itabe H.
  • Journal Title: Proteomics 7 Pages: 2132-2141
• [Journal Article] Involvement of long chain acyl-CoA synthetase in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7 (2007)
  • Author(s): Fujimoto Y, Itabe H, Kinoshita T, Homma KJ, Onoduka J, Mori M, Yamaguchi S, Makita M, Higashi Y, Yamashita A, Takano T.
  • Journal Title: J. Lipid Res. 48 Pages: 1280-1292
• [Presentation] Structure and generation of plasma oxidized LDL during the atherogenesis (2008)
  • Author(s): H. Itabe.
  • Organizer: Lipid Peroxidation 2008
  • Place of Presentation: 軽井沢
  • Year and Date: 20081000
• [Presentation] Behavior of plasma oxidized LDL levels during the early stage of atherogenesis in apolipoprotein E knockout mice (2007)
  • Author(s): H. Itabe.
  • Organizer: Oxidative Stress Summit
  • Place of Presentation: 大阪
  • Year and Date: 20070700
• [Presentation] Atherosclerosis and inflammation: a perspective through oxidized low-density lipoprotein (2007)
  • Author(s): H. Itabe.
  • Organizer: The 1st International Symposium on Development of Anti-inflammatory Drugs
  • Place of Presentation: Gyeongsan, Korea
  • Year and Date: 20070700
• [Presentation] Induction of intracellular lipid droplet proteins by lipids in pathological conditions (2007)
  • Author(s): H. Itabe, Y. Masuda, N. Sasabe, K. Kitazato, K. Takahashi, J. Aoki, H. Arai, and T. Takano.
  • Organizer: The 3rd International Conference on Phospholipase A_2 and Lipid Mediators
  • Place of Presentation: Sorrento, Italy
  • Year and Date: 20070500