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2007 Fiscal Year Final Research Report Summary

Anti-inflammatory effects of anti-insulin resistant drugs and monocyte functional analysis in visceral obesity

Research Project

Project/Area Number 18591013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

SATOH Noriko  Department of Clinical Research, National Hospital Organization Kyoto Medical Center, Kyoto Medical Center, Clinical Research Institute, Division of Diabetic Center, Head of Laboratory of Clinical Metabolism and Nutrition (80373512)

Co-Investigator(Kenkyū-buntansha) OGAWA Yoshihiro  Tokyo Medical and Dental University, Medical Research Institute, Department of Molecular Medicine and Metabolism, 教授 (70291424)
HASEGAWA Koji  Kyoto Medical Center, Clinical Research Institute, Head of Division of Translational Research (50283594)
Project Period (FY) 2006 – 2007
KeywordsInternal Medicine / Diabetes Mellitus / Gene / Insulin Resistance / Function of Monocyte / Obesity
Research Abstract

In the present study, to elucidate the molecular mechanisms of adipocyte-macrohphage interaction, we examined the relationship between adipocytokine dysregulation and the function of monocyte and the effect of anti-insulin resistant agents on the function of monocyte in the obesity and metabolic syndrome.
1. Examination using the THP-1 cell : In THP-1 cell, the incubation with of PPAR ligand ; TZDs(Pioglitazone 6μM) for 24 hours significantly decreased the expression of IL-6 and MMP-9 and the administration of EPA 50 μM for 24 hours significantly decreased CD14, TNFα, MCP-1, MMP-9 and TLR4 and increased adiponectin.
2. Examination using the human monocyte : We examined monocyte function after separating peripheral blood monocyte cells by MACS or Ficoll-Paque method from blood in control, obesity and diabetes. (1) The expressions of TNF-α, IL-6 and MCP-1 detected by real-time PCR in monocyte were higher in obesity and diabetes compared to control. (2) there is no significant difference between the expression and activity of CD14, a specific marker of monocyte, detected by FACS between control and obesity, however in diabetic patients the expression and activity of CD14 and inactive M2 Macrophage was significantly lower. (3) Administrating TZDs for 3 months, the expression of TNF-α and CD14 activity were improved
3. Clinical Study : We revealed that highly purified EPA reduces small, dense LDL(sdLDL), remnants, and CRP(Diabetes Care 27 : 144, 2007) and increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of obese-related adipose tissue inflammation(ATVB 27 : 1918, 2007).

  • Research Products

    (27 results)

All 2008 2007 Other

All Journal Article (14 results) (of which Peer Reviewed: 7 results) Presentation (10 results) Book (3 results)

  • [Journal Article] 3-month changes in bone turnover markers and bone mineral density response to raloxifene in Japanese postmenopausal women with osteoporosis.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      J Bone Miner Metab 26

      Pages: 178-184

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Efficacy of combined treatment with raloxifene and alfacalcidol on bone density and biochemical markers of bone turnover in postmenopausal osteoporosis.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr J 55

      Pages: 127-134

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Increased bone turnover in patients with hypercholesterolemia.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr J 55

      Pages: 143-151

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Association between baseline values of bone turnover markers and bone mineral density and their response to raloxifene treatment in Japanese postmenopausal women with osteoporosis.2008

    • Author(s)
      Majima t, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr J 55

      Pages: 41-48

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 3-month changes in bone turnover markers and bone mineral density response to raloxifene in Japanese postmenopausal women with osteoporosis.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Sato N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      J Bone Miner Metab 26

      Pages: 178-184

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Efficacy of combined treatment with raloxifene and alfacalcidol on bone density and biochemical markers of bone turnover in postmenopausal osteoporosis.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Satoh N. Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr 55

      Pages: 127-134

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increased bone turnover in patients with hypercholesterolemia.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr 55

      Pages: 143-151

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association between baseline values of bone turnover markers and bone mineral density and their response to raloxifenetreatment in Japanese postmenopausal women with osteoporosis.2008

    • Author(s)
      Majima T, Komatsu Y, Shimatsu A. Satoh N. Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Endocr 55

      Pages: 41-81

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoproteinparticles, and CRP in metabolic syndrome.2007

    • Author(s)
      N.Satoh, A.Shimatsu, K.Kotani, N.Sakane, K.Yamada, T.Suganami, H.Kuzuya, Y.Ogawa.
    • Journal Title

      Diabetes Care 27

      Pages: 144-146

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects.2007

    • Author(s)
      M.Itoh, T.Suganami, N.Satoh, K.Tanimoto-Koyama, X.Yuan, M.Tanaka, H.Kawano, T.Yano, S.Aoe, M.Takeya, A.Shimatsu, H.Kuzuya, Y.Kamei, Y.Ogawa.
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 1918-1925

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Short-term effects of pitavastatin on biochemical markers of bone turnover in patients with hypercholesterolemia.2007

    • Author(s)
      Majima T, Shimatsu A, Komatsu Y, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Intern Med 46

      Pages: 1967-1973

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Purified eicosapentaenoic acid reduces small denseLDL, remnant lipoproteinparticles, and CRP in metabolic syndrome.2007

    • Author(s)
      N. Satoh, A. Shimatsu, K. Kotani, N. Sakane, K. Yamada, T. Suganami, GH. Kuzuya, Y. Ogawa.
    • Journal Title

      Diabetes Care 27

      Pages: 144-146

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects.2007

    • Author(s)
      M. Itoh, T. Suganami, K. Satoh, K. Tanimoto-Koyama, X. Yuan, M, Tanaka, H Kawano, T Yano, S Aoe, M Takeya, A Shimatsu, H Kuzuya, Y Kamei, Y Ogawa.
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 1918-1925

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Short-term effects of pitavastatin on biochemical markers of bone turnover in patients with hypercholesterolemia.2007

    • Author(s)
      Majima T, Shimatsu A, Komatsu YSatoh N. Fukao A, Ninomiya K, Matsumura T, Nakao K.
    • Journal Title

      Intern Med 46

      Pages: 1967-1973

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Increased Plasma adiponectin and reduced arterial stiffness by short-term treatment with highly purified eicosapentaenoic acid in metabolic syndrome.2008

    • Author(s)
      Noriko Satoh, Hajime Yamakage, Michiyo Kawahara, Sayaka Shimada, Kazunori Yamada, Akira Shimatsu, Koji Hasegawa
    • Organizer
      1st International Conference on Drug Design and Discovery
    • Place of Presentation
      ドバイ
    • Year and Date
      20080200
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Increased plasma adiponectin and reduced arterial stiffness by short-term treatment with highly purified eicosapentaenoic acid in metabolic syndrome.2008

    • Author(s)
      Noriko Satoh, Hajime Yamakage, Michiyo Kawahara, Sayaka Shimada, Kazunori Yamada, Akira Shimatsu, Koji Hasegawa.
    • Organizer
      1st International Conference on Drug Design and Discovery
    • Place of Presentation
      Dobai
    • Year and Date
      20080000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] メタボリックシンドロームにおけるEPAの心血管リスク軽減と抗動脈硬化作用2007

    • Author(s)
      佐藤哲子、安藤理子、嶋田清香、山陰一、服部正和、山田和範、島津章
    • Organizer
      第44回日本糖尿病学会近畿地方会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      20071100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] an α-glucosidase inhibitor,reduces Systemic Inflammation,Adhesion Molecule and Atherosclerosis through improvement of the Postprandial State in Obese Type2 Diabetes2007

    • Author(s)
      N.Satoh, A.Shimatsu, K.Yamada, Y.Ogawa
    • Organizer
      American Diabetes Association
    • Place of Presentation
      シカゴ・USA
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] メタボリックシンドロームの動脈硬化進展に関わる心血管リスク・炎症指標の検討2007

    • Author(s)
      佐藤哲子、島津章、山田和範、葛谷英嗣
    • Organizer
      第80回日本内分泌学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20070600
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] メタボリックシンドロームにおけるEPAの抗動脈硬化作用-リポ蛋白異常、アディポサイトカインと動脈硬化指標の検討-2007

    • Author(s)
      山陰一、佐藤哲子、小谷和彦、服部正和、山田和範、葛谷英嗣、島津章
    • Organizer
      第50回日本糖尿病年次学術集会
    • Place of Presentation
      仙台
    • Year and Date
      20070500
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Anti-Atherogenic Effects of EPA in Metabolic Syndorme2007

    • Author(s)
      Noriko Satoh, Satoko Ando, Sayaka Shimada, Hajime Yamakage, Masakazu Hattori, Kazunori Yamada, Akira Shimatsu.
    • Organizer
      44th Nippon Tounyoubyou Gakkai Kinki
    • Place of Presentation
      Osaka
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] an α-glucosidase inhibitor, reduces Systemic Inflammation, Adhesion Molecule and Atherosclerosis through improvement of the Postprandial State in Obese Type 2-Diabetes2007

    • Author(s)
      Noriko Satoh, Akira Shimatsu, Kazunori Yamada, Yoshihiro Ogawa.
    • Organizer
      American Diabetes Association
    • Place of Presentation
      Chicago
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Ezamination of the Risks of CVD and Inflammation Marker Regarding on Atherosclerosis in Metabolic Syndrome

    • Author(s)
      Noriko. Satoh, Akira. Shimatsu, Kazunori. Yamada, Hideshi Kuzuya
    • Organizer
      80th Nippon Naibunpitsu Gakkai
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Anti-Atherogenic Effects of EPA in Metabolic Syndrome

    • Author(s)
      Hajime Yamakaee, Noriko Satoh, Kazuhiko Kotani, Masakazu Hattori, Kazunori Yamada, Hideshi Kuzuya, Akira Shimatsu
    • Organizer
      50th Nippon Tounyoubyou Gakkai
    • Place of Presentation
      Sendai
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 肥満モデルマウスおよび肥満症例における高純度EPA製剤のアディポネクチン分泌促進効果について2008

    • Author(s)
      伊藤美智子、菅波孝祥、佐藤哲子、小川佳宏, ほか
    • Total Pages
      3
    • Publisher
      動脈硬化予防
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] レプチンとメタボリックシンドローム2008

    • Author(s)
      佐藤哲子、小川佳宏
    • Total Pages
      8
    • Publisher
      Vascular Medicine
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 脂肪細胞由来炎症性サイトカインと動脈硬化2007

    • Author(s)
      佐藤哲子、小川佳宏
    • Total Pages
      9
    • Publisher
      Adipo Science
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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