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Protective role of an adipocyte-derived factor, adiponectin, on the development of atherosclerotic vascular disease

Research Project

Project/Area Number 10557100
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Endocrinology
Research InstitutionOsaka University

Principal Investigator

FUNAHASHI Tohru  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (60243234)

Co-Investigator(Kenkyū-buntansha) OHMOTO Yasuichi  Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltd., Chief Researcher, 徳島研究所, 主任研究員
KIHARA Shinji  Osaka University Hospital, Medical Stuff, 医学部・附属病院, 医員
NAKAMURA Tadashi  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (90252668)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsobesity / visceral fat / life style-related diseases / atherosclerosis / adiponectin
Research Abstract

Overnutrition by high calorie intake and low physical activity causes obesity, which is a common risk factor for atherosclerotic vascular diseases. Although adipose tissue has been regarde as an organ passively storing excess energy as fat, recent researches explored that adipose tissue secretes a variety of biologically active molecules called adipocytokines, which contribute to the development of complications in obesity.
In this study, we investigated the role of a novel adipose-specific protein, adiponectin on the development of atherosclerotic vascular diseases. The expression of adiponectin mRNA was restricted in adipose tissue and the protein was abundantly present in normal human plasma with the range of 5-10 μg/ml. Plasma concentration of adiponectin was negatively correlated with BMI while it was adipose-specific. The interaction of adiponectin with vascular components was investigated in vivo and in vitro. Adiponectin accumulated in the injured vascular walls but not in the intact vessels. In cultured vascular endothelial cells, adiponectin suppressed the attachment of monocytes to cells, The suppression was caused by the decreased expression of VCAM-1 and ICAM-1 on the cell surface. Plasma levels of adiponectin were decreased in the patients with coronary artery disease even when the BMIs were adjusted Thus, the measurement of plasma adiponectin level may have a potential usefullness for assessment of coronary risk, We also analyzed the genomic structure and mutations in human adiponectin gene. Human adiponectin gene was located on chromosome 3q with 3 exons. We identified a missense mutation in a subject with decreased plasma adiponectin and coronary artery disease. Adiponectin specifically secreted from adipose tissue may have a role in protection against atherosclerosis and decreased plasma adiponectin in obesity may lead to atherosclerotic vascular diseases.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Takahashi M, Arita Y, Yamagata K, et al.: "Genomic structure and mutations in adipose-specific gene, adiponectin"Int. J. Obes. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto Y, Arita Y, Nishida M, et al.: "An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls"Horm. Metab. Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotta K, Matsukawa Y, Nishida M, et al.: "Mutation in bombesin receptor subtype-3 gene is not a major cause of obesity in the Japanese"Horm. Metab. Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ouchi N, Kihara S, Arita Y, et al.: "Novel modulator for endothelial adhesion molecules : adipocyte-derived plasma protein adiponectin"Circulation. 100. 2473-2476 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Funahashi T, Nakamura T, Shimomura I, et al.: "Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity"Intern. Med.. 38. 202-206 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Arita, S. Kihara, N. Ouchi, M. Takahashi, et al.: "Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity"Biochem. Biophys. Res. Commun.. 257. 79-83 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Yoshizumi, T. Nakamura, M. Yamane, W. Isiam.A.H.M., et al.: "A standardized technique for the measurement of abdominal fat based on computed tomography"Radiology. 211. 283-286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Kuriyama, S. Yamashita, I. Shimomura, T. Hunahashi, et al.: "Enhanced expression of hepatic acyl-CoA synthetase and microsomal triglyceride transfer protein mRNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation"Hepatology. 27. 562-557 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kihara, N. Ouchi, T. Funahashi, E. Shinohara, et al.: "Troglitazone enhances glucose uptake and inhibits mitogen-activated protein kinase in human aortic smooth muscle cells"Atherosclerosis. 136. 163-168 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] E. Shinohara, S. Kihara, N. Ouchi, T. Funahashi, et al.: "Troglitazone suppresses intimal formation following baloon injury in insulin-resistant Zacker fatty rats"Atherosclerosis. 136. 275-279 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F. Matsuura, S. Yamashita, T. Nakamura, M. Nishida, et al.: "Effect of visceral fat accumulation on uric acid metabolism in male obese"Metabolism. 47. 929-933 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuzawa Y, Funahashi T, Nakamura T: "Molecular mechanism of metabolic syndrome X : Contribution of adipocytokines adipocyte-derived bioactive substances"Annals of the New York Academy of Sciences. 892. 146-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mitsuzawa Y, Funahashi T, Kuriyama H, Kihara S: "Common Disease : Genetic and Pathogenetic Aspects of Multifactorial Diseases"Elsevier, Amsterdam. 37-43 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuriyama H, Yamashita S, Shimomura I, Funahashi T, Ishigami M, Aragane K, Miyaoka K, Nakamura T, Takemura K, Man Z, Toide K, Nakayama N, Fukuda Y; Lin: "Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation."Hepatology. 27. 557-562 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinohara E, Kihara S, Ouchi N, Funahashi T, Nakamura T, Yamashita S, Kameda-Takemura K, Matsuzawa Y.: "Troglitazone suppresses intimal formation following balloon injury in insulin-resistant Zucker fatty rats."Atherosclerosis. 136. 275-279 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kihara S, Ouchi N, Funahashi T, Shinohara E, Tamura R, Yamashita S, Matsuzawa Y.: "Troglitazone enhances glucose uptake and inhibits mitogen-activated protein kinase in human aortic smooth muscle cells."Atherosclerosis. 136. 163-168 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura F, Yamashita S, Nakamura T, Nishida M, Nozaki S, Funahashi T, Matsuzawa Y.: "Effect of visceral fat accumulation on uric acid metabolism in male obese subjects : visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity."Metabolism. 47. 929-933 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshizumi T, Nakamura T, Yamane M, Islam AH, Menju M, Yamasaki K, Arai T, Kotani K, Funahashi T, Yamashita S, Matsuzawa Y.: "Abdominal fat : standardized technique for measurement at CT."Radiology. 211. 283-286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y.: "Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity."Biochem. Biophys. Res. Commun.. 257. 79-83 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y.: "Novel modulator for endothelial adhesion molecules : adipocyte-derived plasma protein adiponectin."Circulation. 100. 2473-2476 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Funahashi T, Nakamura T, Shimomura I, Maeda K, Kuriyama H, Takahashi M, Arita Y, Kihara S, Matsuzawa Y.: "Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity."Intern.Med. 38. 202-206 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, Shimomura I, Hotta K, Kuriyama H, Kihara S, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y: "Genomic structure and mutations in adipose-specific gene, adiponectin."Int. J. Obes. 2000. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotta K, Matsukawa Y, Nishida M, Kotani K, Takahashi M, Kuriyama H, Nakamura T, Wada K, Yamashita S, Funahashi T, Matsuzawa Y: "Mutation in Bombesin Receptor Subtype-3 Gene is not a Major Cause of Obesity in the Japanese."Horm. Metab. Res. 2000. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto Y, Arita Y, Nishida M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y.: "An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls."Horm. Metab. Res. 2000. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuzawa Y, Funahashi T, Nakamura T : Molecular mechanism of metabolic syndrome X: "Contribution of adipocytokines, adipocyte-derived bioactive substances.."Annals of the New York Academy of Sciences. 892. 146-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuzawa Y, Funahashi T, Kuriyama H, Kihara S: "Molecular mechanism of obesity-related diseases : importance of adipocytokine."In Common Disease : Genetic and Pathogenetic Aspects of Multifactorial Diseases. Imura H, Kasuga M, Nakao K eds, Elsevier, Amsterdam. 37-43 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi M,Arita Y,Yamagata K,et al.: "Genomic structure and mutations in adipose-specific gene,adiponectin"Int. J. Obes. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto Y,Arita Y,Nishida M,et al.: "An adipocyte-derived plasma protein,adiponectin,adheres to injured vascular walls"Horm. Metab. Res.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hotta K,Matsukawa Y, Nishida M,et al.: "Mutation in bombesin receptor subtype-3 gene is not major cause of obesity in the Japanese"Horm. Metab. Res.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ouchi N,Kihara S, Arita Y et al.: "Novel modulator for endothelial adhesion molecules : adipocyte-derived plasma protein adiponectin"Circulation. 100. 2473-2476 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Funahashi T,Nakamura T,Shimomura I,et al.: "Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity"Intern. Med. 38. 202-206 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Arita,S. Kihara,N. Ouchi,M. Takahashi et al.: "Paradoxical decrease of an adipose-specific protein,adiponectin,in obesity"Biochem. Biophys. Res. Commun.. 257. 79-83 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Yoshizumi,T. Nakamura,M. Yamane,W. Islam. A. H. M.,et al.: "A standardized technique for the measurement of abdominal fat based on computed tomography"Radiology. 211. 283-286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuzawa Y,Funahashi T,Nakamura T: "Molecular mechanism of metabolic syndrome X : Contribution of adipocytokines,adipocyte-derived bioactive substances"Annals of the New York Academy of Sciences. 892. 146-154 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuzawa Y,Funahashi T,Kuriyama H,Kihara S: "Common Disease : Genetic and Pathogenetic Aspects of Multifactorial Diseases"Elsevier,Amsterdam. 7 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Arita,S.Kihara,N.Ouchi,M.Takahashi et al.: "Paradoxical decrease of an adipose-specific protein,adiponectin,in obesity" Biochem.Biophys.Res.Commun.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Yoshizumi,T.Nakamura,M.Yamane,W.Isiam.A.H.M.,et al.: "A standardized technique for the measurement of abdominal fat based on computed tomography" Radiology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kuriyama,S.Yamashita,I.Shimomura,T.Funabashi,et al.: "Enhanced expression of hepatic acyl-CoA synthetase and microsomal triglyceride transfer protein mRNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation" Hepatology. 27(2). 562-557 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Kihara,N.Ouchi,T.Funabashi,E.Shinohara,et al.: "Troglitazone enhances glucose uptake and inhibits mitogen-activated protein kinase in human aortic smooth muscle cells" Atherosclerosis. 136(1). 163-168 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] E.Shinohara,S.Kihara,N.Ouchi,T.Funahashi,et al.: "Troglitazone suppresses intimal formation following balloon injury in insulin-resistant Zucker fatty rats" Atherosclerosis. 136(2). 275-279 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Matsuura,S.Yamashita,T.Nakamura,M.Nishida,et al.: "Effect of visceral fat accumulation on uric acid metabolism in male obese subjects:visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity" Metabolism. 47(8). 929-933 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Nakagawa,S.Nozaki,M.Nishida,J.M.Yakub,et al.: "Oxidized LDL increases and interferon-gamma decreases expression of CD36 in human monocvte-derived macrophages" Arterioscler.Thromb.Vasc.Biol.18(8). 1350-1357 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Maruyama,Y.Miyake,T.Yamamura,S.Tajima,et al.: "A novel point mutation in a splice accceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia:an unexpected absence of exon skipping" Human Mutation. 12. 480-483 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Matsuura,S.Yamashita,H.Hirano,M.Ishigami,et al.: "Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia-possible pathogenesis of nerobiotic xanthogranuloma-" Atherosclerosis. (in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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