• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular pathogenesis of vascular disease by adipocyte-derived factors, adipocytokines

Research Project

Project/Area Number 10671035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionOsaka University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) KIHARA Shinji  Osaka University Hospital, Medical Stuff, 医学部・附属病院, 医員
NAKAMURA Tadashi  Osaka University Graduate School of Medicine, 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
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywordsobesity / visceral fat / life style-related diseases / atherosclerosis
Research Abstract

Atherosclerotic cardiovascular complications are the major causes of morbidity and mortality in obesity. Traditionally adipose tissue has been considered to be as an organ that passively stores excess energy as fat. Substantial research has explored the notion 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 adipocytokines on the development of atherosclerotic vascular diseases. We have isolated a cDNA for adiponectin which is a novel adipose-specific protein belonging to the collectin family. We developped ELISA system for the measurement of plasma concentration of adiponectin. The protein was present abundantly in the circulation accounting for approximately 0.01% of total plasma protein. Although the expression of adiponectin mRNA is restricted in adipose tissue, its plasma concentrations were decreased in obesity. We tested the interaction of adiponectin to vascular components in vivo and in vitro. When the endothelium of the carotid arteries was injured by a balloon catheter in rat, adiponectin accumulated in the vascular walls. Adiponectin suppressed the attachment of monocytes to vascular endothelial cells, which is an early event in atherosclerotic vascular change. Plasma levels of adiponectin were decreased in the patients with coronary artery disease even when BMIs were matched. 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 vascular damage 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 MC, Wetterau JR, Matsuzawa Y.: "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, M: "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(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. (in press). (2000)

    • 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.. (in press). (2000)

    • 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."Annal's 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 a 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. 37-43 (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.Islam.A.H.M.,et al: "A standardized technique for the measurement of abdominal on computed tomography" Radiology. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kuriyama,S.Yamashita,I.Shimomura,T.Funahashi,et al: "Enhanced expression of hepatic acy-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.Funahashi,B.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,M.Yakub,et al.: "Oxidized LDL increases and interferon-gamma decreases expression of CD36 in human monocyte-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 I of the human low density lipoprotein receptor gene whlch causes severe hypercholesterolemis:an unexpected absence of exon skippinng" Human Mutation. 12. 480-483 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Matsuutra,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

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi