1999 Fiscal Year Annual Research Report

内蔵脂肪特異的遺伝子の同定とその臨床応用

Research Project

Project/Area Number	10557101
Research Institution	Osaka University
Principal Investigator	松澤佑次大阪大学, 医学系研究科, 教授 (70116101)
Co-Investigator(Kenkyū-buntansha)	中村正大阪大学, 医学系研究科, 助手 (90252668) 舟橋徹大阪大学, 医学系研究科, 助手 (60243234) 山下静也大阪大学, 医学系研究科, 講師 (60243242) 中澤宏住友化学株式会社, 生命工学研究所, 研究員木原進士大阪大学, 医学部・附属病院, 医員
Keywords	肥満 / 内臓脂肪 / 生活習慣病 / 動脈硬化
Research Abstract	現代社会において体脂肪の過剰蓄積は糖尿病、血管病等の様々な病態の基盤となっている。体脂肪蓄積による病態の発症は一様ではなく脂肪の蓄積部位、脂肪分布と密接に関連している。すなわち皮下脂肪よりも腹腔内内臓脂肪の蓄積が上記の病態と深く関わっている。本研究の目的は内臓脂肪と皮下脂肪の生物学的差異を分子レベルで明らかにし、臨床に応用しようとするものである。内臓脂肪発現遺伝子の大規模シークエンス解析により、皮下脂肪がリボゾーム蛋白や細胞骨格蛋白等の細胞維持に関わる比較的静的な遺伝子を多く発現していたのに対し、内臓脂肪は多くの生理活性物質を含む分泌蛋白遺伝子の発現が優位であった。本年度は私達が新しく発見した脂肪組織特異的遺伝子、adiponectin とclone 085につき内臓脂肪蓄積との関連において検討した。adiponectin は脂肪細胞特異的な分泌蛋白であるにもかかわらず、体脂肪蓄積、特に内臓脂肪蓄積時に血中濃度が低下した。冠動脈疾患患者においては肥満度で補正しても血中濃度の著しい低下を示し、動脈硬化の指標として用いうることが示された。本分子は血管内皮細胞への単球接着抑制や、平滑増殖抑制などの抗動脈硬化作用を有し、新たな動脈硬化治療開発への可能性が示された。clone 085は differential display により得られた遺伝子で、体脂肪過剰蓄積時に特に内臓脂肪において発現増加が認められた。血中濃度測定法を開発し検討したところ、clon 085産物の血中濃度は皮下脂肪量とは相関しなかったが、内臓脂肪量と良好な正相関関係が得られ、内臓脂肪量測定のパロメーターとして用いうると考えられた。

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] T. Yoshizumi,T. Nakamura,M. Yamane,W. Islam. A. H. M., et al.: "A standardizes technique for the measurement of abdominal fat based on computed tomography"Radiology. 211. 263-286 (1999)
[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. 79-85 (1999)
[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)
[Publications] Inoue S,Fukurda 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)
[Publications] Kayanoki Y,Higashiyama S,Suzuki K et al.: "The requirement of both intracellular reactive oxygen species and intracellular calcium elevation for the induction of heparin-binding EGF-like growth factor in vascular endothelial cells and smooth muscle cells"Biochem. Biophys. Res. Commun.. 259. 50-55 (1999)
[Publications] Kiso S,Kawata S,Tamura S: "Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on on DNA synthesis of hepatocytes in normal mouse liver"Biochem. Biophys. Res. Commun.. 259. 685-687 (1999)
[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)
[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 with CD3 deficiency"Mol Cell Biochem. 192 : 129-135,1999. 192. 129-135 (1999)
[Publications] Hirano K,Yamashita S,Nakagawa Y et al.: "Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions"Cric Res. 85. 108-116 (1999)
[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 in human atherosclerotic aorta"Arterioscler Thromb Vasc Biol. 19. 1333-1339 (1999)
[Publications] Yang Q,Yamagata K,Yamamoto K, et al.: "Structure/function studies of hepatocyte nuclear factor -1alpha,a diabetes -associated transcription factor"Biochem. Biophys. Res. Commun.. 266. 196-202 (1999)
[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)
[Publications] Yoshiuchi I, Yamagata K, Yang Q et al.: "Three new mutations in the hepatocyte nuclear factor-1 alpha gene in Japanese subjects with diabetes mellitus : clinical features and functional characterization"Diabetologia. 42. 621-626 (1999)
[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"Diabetologia. 42. 1332-1340 (1999)
[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 mellitus"Diabetologia. 42. 574-578 (1999)
[Publications] Yamada S,Zhu Q,Aihara Y et 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"Diabetologia. 43. 121-124 (2000)
[Publications] Imagagawa A Hanafusa T,Miyagawa J et al.: "A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies"N Engl J Med. 342. 301-307 (2000)
[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)
[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)
[Publications] Takahashi M,Arita Y,Yamagata K et al.: "Genomic structure and mutations in adipose-specific gene,adiponectin"Int. J. Obes.. (in press). (2000)
[Publications] Funahashi T,Takamura 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)
[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)
[Publications] Matsuzawa Y,Funahashi T,Kuriyama H,Kihara S: "Common Disease : Genetic and Pathogenetic Aspect of Multifactional Diseases"Molecular mechanism of obesity-related diseases : importance of adipocytokine. 7 (1999)

1999 Fiscal Year Annual Research Report

内蔵脂肪特異的遺伝子の同定とその臨床応用

Principal Investigator

松澤 佑次 大阪大学, 医学系研究科, 教授 (70116101)

Research Products

[Publications] T. Yoshizumi,T. Nakamura,M. Yamane,W. Islam. A. H. M., et al.: "A standardizes technique for the measurement of abdominal fat based on computed tomography"Radiology. 211. 263-286 (1999)

[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. 79-85 (1999)

[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)

[Publications] Inoue S,Fukurda 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)

[Publications] Kiso S,Kawata S,Tamura S: "Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on on DNA synthesis of hepatocytes in normal mouse liver"Biochem. Biophys. Res. Commun.. 259. 685-687 (1999)

[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)

[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 with CD3 deficiency"Mol Cell Biochem. 192 : 129-135,1999. 192. 129-135 (1999)

[Publications] Hirano K,Yamashita S,Nakagawa Y et al.: "Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions"Cric Res. 85. 108-116 (1999)

[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 in human atherosclerotic aorta"Arterioscler Thromb Vasc Biol. 19. 1333-1339 (1999)

[Publications] Yang Q,Yamagata K,Yamamoto K, et al.: "Structure/function studies of hepatocyte nuclear factor -1alpha,a diabetes -associated transcription factor"Biochem. Biophys. Res. Commun.. 266. 196-202 (1999)

[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)

[Publications] Yoshiuchi I, Yamagata K, Yang Q et al.: "Three new mutations in the hepatocyte nuclear factor-1 alpha gene in Japanese subjects with diabetes mellitus : clinical features and functional characterization"Diabetologia. 42. 621-626 (1999)

[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"Diabetologia. 42. 1332-1340 (1999)

[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 mellitus"Diabetologia. 42. 574-578 (1999)

[Publications] Yamada S,Zhu Q,Aihara Y et 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"Diabetologia. 43. 121-124 (2000)

[Publications] Imagagawa A Hanafusa T,Miyagawa J et al.: "A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies"N Engl J Med. 342. 301-307 (2000)

[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)

[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)

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

[Publications] Funahashi T,Takamura 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)

[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)

[Publications] Matsuzawa Y,Funahashi T,Kuriyama H,Kihara S: "Common Disease : Genetic and Pathogenetic Aspect of Multifactional Diseases"Molecular mechanism of obesity-related diseases : importance of adipocytokine. 7 (1999)

松澤佑次大阪大学, 医学系研究科, 教授 (70116101)