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1999 Fiscal Year Final Research Report Summary

Identification of adipose-specific genes and teir clinical significance

Research Project

Project/Area Number 10557101
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

MATSUZAWA Yuji  Graduate School of Medicine, Osaka University, Professor, 医学系研究科, 教授 (70116101)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tadashi  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (90252668)
FUNAHASHI Tohru  Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (60243234)
YAMASHITA Shizuya  Graduate School of Medicine, Osaka University, Lecturer, 医学系研究科, 講師 (60243242)
NAKAZAWA Hiroshi  Biotechnical laboratory, Sumitomo chemical company, Ltd. Research Director, 生命工学研究所, 研究員
KIHARA Shinji  Osaka University Hospital, Medical Stuff, 医学部・附属病院, 医員
Project Period (FY) 1998 – 1999
Keywordsobesity / visceral fat / life style-related diseases / atherosclerosis
Research Abstract

Accumulation of excess body fat has become a common basis for the development of non-insulin dependent diabetes mellitus (NIDDM) and atherosclerotic vascular diseases (AVD). Body fat distribution is a independent r the risk for above diseases. Deposition of intra-abdominal viscreal fat rather than subcutaneous fat closely relates to the development of NIDDM and AVD. The aim of this study is to clarify the biological difference between subcutaneous and visceral fat tissues and to apply the data to clinical medicine.
By the comparison of the gene expression profiles of subcutaneous and visceral fat tissues, subcutaneous fat has been revealed predominantly to express "static" genes for the proteins maintaining fundamental cellular functions including ribosomal protein and cytoskeleton proteins. On the other hand, visceral fat predominantly expressed the genes for a variety of secretory proteins with biological activities.
We focused on two genes, that is, adiponectin, which was obtained by … More a large-scale-random sequencing of adipose-tissue cDNA library and clone 085, which was isolated by diferential display technique. Adiponectin is plasma protein specifically produced and secreted from adipose tisuue. Plasma levels of adiponectin, however, decreased in the obese subjects, especially those with visceral fat accumulation. Marked reduction of plasma adiponectin concentration was observed in he patients with coronary artey disease compaired with BMI-matched conrols. Therefore, decreased plasma adponectin has been proven to be a potential risk for coronary artery disease. The proein showed anti-atherogenic properties, including suppresion of monocyte-adhesion to endothelial cells and proliferation of vascular diseases.
The product of clone 085 belonged to hematopoietic factors The expression of mRNA for clone 085 increased in visceral fat during the development of obesity. Plasma levels of clone 085 products increased in paralel with the amount of visceral fat in mice. In humans, plasma 085 level was closely correlated with the amount of visceral fat but not with subcutaneous fat.
In this study, we investigated in the visceral fat derived factors. The measurement of plasma levels of these visceral fat derived factors will be a clue for understanding the pathogenesis of diseases accompanied by visceral fat obesity. Less

  • Research Products

    (53 results)

All Other

All Publications (53 results)

  • [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
  • [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
  • [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
  • [Publications] Matsuura F, Yamashita S, Nakamura T, et al.: "Effect of visceral fat accumulation on uric acid metabolism in male obese subjjects : 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(和文)」より
  • [Publications] T. Yoshizumi, T. Nakamura, M. Yamane, W. ISAM. A. H. M. et al.: "A standardized technique for the measurement of abdominal fat based on computed tomography"Radiology. 211. 263-286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Arita, S. Kihara, N. Ouchi, M. Takahashi et al.: "Paradoxial decrease of an adipose -specific protein, adiponectin, in obesity"Biochem, Biophys. Res. Commun.. 257. 79-85 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ouchi N, Kihara S. Arita Yet 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
  • [Publications] noue S, Fukuda K, Kudara et al.: "Augmented growth response to IGF-1 via increased IRS-1 In Chinese hamster ovary cells expressing kinase-negative insulin receptors"Diabetologia. 42. 763-772 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kayanoki Y, Higashiyama S, Suzuki K, et al.: "The requirement of both intracellular reactive oxygen species and intracellular calcuim evelation for the induction of heparin-binding EGF-like growth factor in vascular"Biochem, Biophys. Res. Commun.. 259. 50-55 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiso S, Kawata S, Tamura S,: "Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on DNA synthesis of hepatocytes in normal mouse liver"Biochem, Biophys. Res. Commun.. 259. 685-687 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kayanoki Y, Kawata S, Yamasaki E: "Reduced nitric oxide production by L-arginine deficiency in lysinuric protein Intolerance exacerbates Intravascular coagulation"Metabolism 48 : 1136-1140, 1999. 46. 1136-1140 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nozaki S, Tanaka T, Yamashita S, et al.: "CD36 mediates long-chain fatty acid transport in human myocardium : complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog In subjects"Mol. Cell Biochem. 192: 129-135. 1999. 192. 129-135 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirano K, Yamashita S, Nakagawa Yet al.: "Expression of human scavenger receptor class B type I In cultured human monocyte-derived macrophages and atherosclerotic lesions"Circ Res. 85. 108-116 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakata A, Nakagawa Y, Nishida M, et al.: "CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages on human atherosclerotic aorta"Arterioscler Thromb Vasc Biol. 19. 1333-1339 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang Q, Yamagata K, Yamamoto K, et al: "Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcripton factor"Biochem, Biophys. Res. Commun.. 266. 196-202 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okita K, Yang Q, Yamagata K, et al: "Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha(HNF-1alpha) and HNF-1beta"Biochem, Biophys. Res. Commun.. 263. 566-569 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiuchi I, Yamagata K, Yang Q, et al.: "Three new mutations in the hepatocyte nuclear factor-1alpha gene In Japanese subjects with diabetes mellitus : clinical features and functional characterization"Diabetlogia. 42. 621-626 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moriwaki M, Itoh N, Miyagawa J, et al.: "Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I diabetes mellitus"Diabetlogia. 42. 1332-1340 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imagawa A, Hanafusa T, Itoh N, et al.: "Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control In patients with recent-onset Type I (Insulin-dependent) diabetes"Diabetlogia. 42. 574-578 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada S, Zhu Q. Aihara Yet al.: "Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 beta and mutation screening In Japanese subjects with maturity-onset diabetes of the young"Diabetlogia. 43. 121-124 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imagawa A, Hanafusa T, Miyagawa J, et al: "A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabeters-related antibodies"N Engl J Med.. 342. 301-307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [Publications] Takahashi Y, Alita Y, Yamagata K et al.: "Genotic 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
  • [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. 38. 202-206 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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. 892. 146-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [Publications] Inoue S, Fukuda K, Kudara T, Igura T, Inui Y, Tamura S, Hanafusa T, Kawata S, Matsuzawa Y.: "Augmented growth response to IGF-1 via increased IRS-1 in Chinese hamster ovary cells expressing kinasenegative insulin receptors"Diabetologia. 42. 763-772 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kayanoki Y, Higashiyama S, Suzuki K, Asahi M, Kawata S, Matsuzawa Y, Taniguchi N.: "The requirement of both intracellular reactive oxygen species and intracellular calcium elevation for the induction of heparinbinding EGF-like growth factor in vascular endothelial cells and smooth muscle cells."Biochem Biophys Res Commun.. 259. 50-55 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiso S, Kawata S, Tamura S, Umeki S, Ito N, Tsushima H, Yamada A, Miyagawa J, Higashiyama S, Taniguchi N, Matsuzawa Y.: "Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on DNA synthesis of hepatocytes in normal mouse liver."Biochem Biophys Res Commun. 259. 683-687 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kayanoki Y, Kawata S, Yamasaki E, Kiso S, Inoue S, Tamura S, Taniguchi N, Matsuzawa Y.: "Reduced nitric oxide production by L-arginine deficiency in lysinuric protein intolerance exacerbates intravascular coagulation."Metabolism. 48. 1136-1140 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nozaki S, Tanaka T, Yamashita S, Sohmiya K, Yoshizumi T, Okamoto F, Kitaura Y, Kotake C, Nishida H, Nakata A, Nakagawa T, Matsumoto K, Kameda-Takemura K, Tadokoro S, Kurata Y, Tomiyama Y, Kawamura K, Matsuzawa Y.: "CD36 mediates long-chain fatty acid transport in human myocardium : complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency."Mol Cell Biochem.. 192. 129-135 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano K, Yamashita S, Nakagawa Y, Ohya T, Matsuura F, Tsukamoto K, Okamoto Y, Matsuyama A, Matsumoto K, Miyagawa J, Matsuzawa Y.: "Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions."Circ Res.. 85. 108-116 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata A, Nakagawa Y, Nishida M, Nozaki S, Miyagawa J, Nakagawa T, Tamura R, Matsumoto K, Kameda-Takemura K, Yamashita S, Matsuzawa Y.: "CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta."Arterioscler Thromb Vasc Biol.. 19. 1333-1339 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang Q, Yamagata K, Yamamoto K, Miyagawa J, Takeda J, Iwasaki N, Iwahashi H, Yoshiuchi I, Namba M, Miyazaki J, Hanafusa T, Matsuzawa Y.: "Structure/function studies of hepatocyte nuclear factor-1 alpha, a diabetes-associated transcription factor."Biochem Biophys Res Commun.. 266. 196-202 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okita K, Yang Q, Yamagata K, Hangenfeldt KA, Miyagawa J, Kajimoto Y, Nakajima H, Namba M, Wollheim CB, Hanafusa T, Matsuzawa Y.: "Human insulin gene is a target gene of hepatocyte nuclear factor-lalpha (HNF-lalpha) and HNF-lbeta."Biochem Biophys Res Commun.. 263. 566-569 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshiuchi I, Yamagata K, Yang Q, Iwahashi H, Okita K, Yamamoto K, Oue T, Imagawa A, Hamaguchi T, Yamasaki T, Horikawa Y, Satoh T, Nakajima H, Miyazaki J, Higashiyama S, Miyagawa J, Namba M, Hanafusa T, Matsuzawa Y.: "Three new mutations in the hepatocyte nuclear factor-lalpha gene in Japanese subjects with diabetes mellitus : clinical features and functional characterization."Diabetologia. 42. 621-626 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moriwaki M, Itoh N, Miyagawa J, Yamamoto K, Imagawa A, Yamagata K, Iwahashi H, Nakajima H, Namba M, Nagata S, Hanafusa T, Matsuzawa Y.: "Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I (insulin-dependent) diabetes mellitus."Diabetologia. 42. 574-578 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imagawa A, Hanafusa T, Itoh N, Waguri M, Yamamoto K, Miyagawa J, Moriwaki M, Yamagata K, Iwahashi H, Sada M, Tsuji T, Tamura S, Kawata S, Kuwajima M, Nakajima H, Namba M, Matsuzawa Y.: "Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus."Diabetologia. 42. 574-578 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada S, Zhu Q, Aihara Y, Onda H, Zhang Z, Yu L, Jin L, Si YJ, Nishigori H, Tomura H, Inoue I, Morikawa A, Yamagata K, Hanafusa T, Matsuzawa Y, Takeda J.: "Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF) -3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young."Diabetologia. 43. 121-124 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imagawa A, Hanafusa T, Miyagawa J, Matsuzawa Y, Osaka IDDM Study Group.: "A novel subtype of type 1 diabetes mellitus characterized by rapid onset and an absence of diabetes-related antibodies."N Engl J Med.. 342. 301-307 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Okamoto Y, Arita Y, Nishida M, Ouchi N, Takahshi 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
  • [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
  • [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
  • [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
  • [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)

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      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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