Project/Area Number |
10557100
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Endocrinology
|
Research Institution | Osaka 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)
|
Keywords | obesity / 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.
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