In vivo molecular imaging analysis of pathophysiology in metabolic syndrome

• Project/Area Number: 20591052
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: YAMASHITA Hiroshi The University of Tokyo, 医学部附属病院, 講師 (50323572)
• Co-Investigator(Kenkyū-buntansha): SUGIURA Seiryo 東京大学, 大学院・新領域創成科学研究科, 特任教授 (10272551) ; FUJITA Hideo 東京大学, 医学部附属病院, 特任准教授 (70327336) ; KATOU Masayoshi 東京大学, 医学部附属病院, 特任臨床医 (40306345) ; NISHIMURA Satoshi 東京大学, 医学部附属病院, 特任助教 (80456136)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: メタボリックシンドローム / 生体分子イメージング / 共焦点顕微鏡 / 慢性炎症 / 免疫 / メタボリック症候群 / 分子イメージング / CD8陽性T細胞 / 脂肪組織 / リモデリング / 肥満 / 内臓肥満 / 生体内分子イメージング / 血管新生 / 脂肪細胞 / VEGF / T細胞 / 炎症細胞

Research Abstract

Metabolic syndrome is a major risk factor of cardiovascular disease and one of the leading causes of death. In adipose tissue of an obese animal, an experimental disease model of human metabolic syndrome, differentiation and hypertrophy of adipose cells as well as chronic inflammation takes place and plays critical role in the pathogenesis. We developed an "in vivo molecular imaging technique", where we could distinguish various types of cells, such as adipose cells, vascular endothelial cells and blood cells including immunocytes, and observe cell-to-cell interactions in adipose tissues of a living animal. We found that large number of CD8+ effector T cells infiltrated into obese adipose and contributed to the macrophage recruitment, which culminated in chronic inflammation in obese tissue. We also clearly showed that "in vivo molecular imaging technique" is a powerful tool to analyze complex cellular interactions in various types of human disease models.

Research Products

• [Journal Article] CD8^+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity (2009)
  • Author(s): Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R.
  • Journal Title: Nature Medicine 15:8 Pages: 914-920
  • Peer Reviewed
• [Journal Article] CD8^+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity (2009)
  • Author(s): Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R
  • Journal Title: Nature Medicine 15:8 Pages: 914-920
  • Peer Reviewed
• [Journal Article] Responses of single-ventricular myocytes to dynamic axial stretching. (2008)
  • Author(s): Nishimura, S, Seo, K, Hosoya, Y, Yamashita, H, and et al.
  • Journal Title: Progress in Biophysics & Molecular Biology 97 Pages: 282-297
  • Peer Reviewed
• [Presentation] In Vivo Molecular Imaging Reveals Multi-cellular Kinetics of Developing Thrombus (2011)
  • Author(s): Nishimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Nagai R
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Adipose Tissue Remodeling and Malfunctioning in Obesity Based on Chronic Inflammation and Abnormal Local Immunity (2011)
  • Author(s): Nishimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Nagai R
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Multi-cellular Kinetics in Thrombosis Visualized by in Vivo Molecular Imaging (Featured Research Session) (2010)
  • Author(s): Nishimura S, Nagasaki M, Manabe I, Yamashita H, Eto K, Nagai R
  • Organizer: 第74回 日本循環器学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Adipose Tissue Remodeling and Chronic Inflammation in Obesity : a Novel Key Player, CD8+ T cells (2010)
  • Author(s): Nishimura S, Nagasaki M, Manabe I, Yamashita H, Eto K, Nagai R
  • Organizer: 第74回 日本循環器学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] In vivo Imaging Reveals Multi-Cellular Kinetics in Inflammatory Diseases : Adipose Tissue Obesity and Thrombosis (2010)
  • Author(s): Nishimura S, Nagasaki M, Manabe I, Yamashita H, Eto K, Nagai R
  • Organizer: 第74回 日本循環器学会総会・学術集会シンポジウム Topic11 分子イメージング法がもたらす循環器研究の進展
  • Place of Presentation: 京都
• [Presentation] Chronic Inflammation, Macrophage Recruitment and CD8+ T Cell Activation in Obese Adipose Tissue Visualized by in vivo Molecular Imaging (2009)
  • Author(s): Nishimura, S, Yamashita, H and et al.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
• [Presentation] Platelet Kinetics in Thrombus Formation, and Inflammatory Status Revealed by in vivo Molecular Imaging (2009)
  • Author(s): Nishimura, S, Yamashita, Hand et al.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
• [Presentation] Is the contractile dysfunction of detubulated cardiomyocytes caused only by the asynchrony of Ca2+ regulation? (2008)
  • Author(s): Nishimura, S, Yamashita, Hand et al.
  • Organizer: 第15回国際心臓研究会日本部総会
  • Place of Presentation: 神奈川
• [Remarks] ホームページ等