Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution Osaka University
2.Research Area Life Sciences
3.Research Field Genetic and Environmental Factors in Diseases Prevalent in Adults and the Elderly:Molecular and Cellular Mechanism of Vascular Complication
4.Term of Project FY 1997 〜 FY 2001
5.Project Number 97L00801
6.Title of Project Molecular Biology of Adipocytes:Studies on Molecular Mechanisms of Fat Accumulation and Vascular Diseases

7.Project Leader
Name Institution,Department Title of Position
Yuji, Matsuzawa Osaka University, Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Touru, Funahashi Osaka University, Graduate School of Medicine Lecturer
Shizuya , Yamashita Osaka University, Graduate School of Medicine Associate Professor
Jun-ichiro, Miyagawa Osaka University, Graduate School of Medicine Lecturer

9.Summary of Research Results

Atherosclerotic vascular diseases are common disorder in the industrial countries in which people are exposed by overnutrition. Accumulation of body fat may contribute to the development of atherosclerosis. This study was planned to clarify the biological characteristics of adipocytes and to identify the molecular link between adipocytes and vascular diseases.
We analyzed the expression profile of adipose tissue. Traditionally, adipose tissue has been regarded as an energy storage organ. However, adipose tissue expressed a variety of the genes for secretory proteins. Those included various complement factorsin immune system, cytokines, growth factors and vasoactive substances such as plasminogen activator inhibitor in fibrinolytic system and heparine biding EGF-like growth factor, which is a potent growth factor for vascular smooth muscle cells. We named these adipocyte-derived bioactive substances as 'adipocytokines'. Dysregulation of adipocytokines might be one of the mechanisms in the development of vascular diseases in overnutirion.
Through the analysis of human fat cDNA library, we identified a novel adipose-derived factor named adiponectin. Adiponectin was produced specifically by adipose tissue and present in circulating plasma with a range of 5-10μg/ml. Plasma levels of adiponectin decreased in obesity in spite of its specific expression in adipose tissue. Adiponectin had anti-atherogenic and anti-diabetic properties. Genetic lack of adiponectin in humans and rodents exhibited insulin resistance and vascular disease. The molecule may be a key factor in the disorders caused by overnutrition. We also identified glycerol channel molecule, aquaporin adipose and apotosis-inducing factor, galectin-12.
Adipocytes synthesize a variety of molecules to maintain homeostasis of the body. Disruption of this self-defense mechanism will lead to human diseases.

10.Key Words

(4)Gene、(5)Biomolecule、(6)Regulation of expression
(7)Medicine、(8)Translational research