Project/Area Number |
13671155
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
|
Research Institution | Osaka University |
Principal Investigator |
KIHARA Shinji Osaka University Graduate School of Medicine. Assistant Professor, 医学系研究科, 助手 (20332736)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tadashi Osaka University Graduate School of Medicine. Assistant Professor, 医学系研究科, 助手 (90252668)
FUNAHASHI Tohru Osaka University Graduate School of Medicine. Instructor, 医学系研究科, 講師 (60243234)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
Keywords | atherosclerosis / visceral fat / visfatin / endothelial cell / monocyte chemotactic protein / tumor necrosis factor / macrophage / coronary artery disease / Visceroadipotropin |
Research Abstract |
Obesity, defined as excess fat accumulation, is the most common cause of atherosclerotic cardiovascular morbidity and mortality in Japan. We have reported that intra-abdominal visceral fat accumulation due to overnutrition and physical inactivity is the common clinical background in the development of atherosclerosis. Based on the findings, we performed a differential display of visceral and subcutaneous fat tissue cDNA libraries, and found visceroadipotropin (renamed to visfatin), a novel secretory protein highly expressed in visceral fat tissue. The visfatin mRNA level was significantly higher in viscerl fat tissue compared with that in subcutaneous fat tissue. The recombinant visfatin protein enhanced the differentiation of adipocyte, suggesting that the molecule contributes to the visceral fat accumulation. In vitro experiments revealed that the recombinant protein stimulated the secretion of monocyte chemotactic protein-1 in the vascular endothelial cells, and tumor necrosis factor-alpha in the monocyte-derived macrophages. Consequently, we are studying the molecular mechanism in the development.of atherosclerosis through endocrine system. In clinical study, the plasma visfatin levels were significantly higher in patients with coronary artery disease (CAD) compared with those in control subjects. Currently, we are enrolling CAD patients to elucidate the clinical significance of this molecule. These results suggest that visfatin contributes to the visceral fat accumulation; and the measurement of the plasma level is helpful to evaluate the CAD risk.
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