1999 Fiscal Year Final Research Report Summary
Molecular pathogenesis of vascular disease by adipocyte-derived factors, adipocytokines
| Project/Area Number |
10671035
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Osaka University |
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Principal Investigator |
FUNAHASHI Tohru Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60243234)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Keywords | obesity / visceral fat / life style-related diseases / atherosclerosis |
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| 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.
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Research Products
(26 results)
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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