NAKAMURA Tadashi Graduate School of Medicine, Osaka University Assistant Professor, 医学系研究科, 助手 (90252668)
FUNAHASHI Tohru Graduate School of Medicine, Osaka University Assistant Professor, 医学系研究科, 助手 (60243234)
YAMASHITA Shizuya Graduate School of Medicine, Osaka University Lecturer, 医学系研究科, 講師 (60243242)
AUWERX Johan パスツール研究所, 主任研究員
|Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Obesity, defined as an overaccumulation of body fat is a basis for most common diseases, including diabetes mellitus, dyslipoproteinemia, hypertension, atherosclerotic vascular diseases, colon cancer and inflammatory bowel disease in the industrial countries. In this study, we investigated the moecular mechanisms of the life-style related diseases through the analyses of the biological properties of intra-abdomial visceral fat tissue with international collaboration.
We analyzed the gene expression profile of subcutaneous and visceral adipose tissues and found that adipose tissue, especially visceral fat is not simply an energy storing organ, but is an endocrine organ expressing a variety of genes for biologically active secretory proteins. Dr. Auwerx's group in Pasteur institute in France analyzed the depot-specific expression of the genes in adipose tissues and revealed several genes predominantly expressing each adipose tissue.
Through the search of adipose-expressed genes, we isolate
d a novel cDNA abundantly specifically expressed in adipose tissue. The gene product, adiponectin was synthesized in adipose tissue and abundantly present in the circulation with the concentration of 5-10 μg/ml. Unexpectedly, plasma adiponectin levels were decreased in obesity, especially in visceral obesity. The protein suppressed adhesion of monocytes to vascular endothelial cells and proliferation of vascular smooth muscle cells in vitro, thus has a potential anti-atherogenic property. Hypoadiponectinemia observed in visceral obesity may play a role in the development of atherosclerotic vascular diseases.
Dr. Auwex's group focused on PPARγ, which is a master regulator of adipocyte-differentiation and elucidated depot-specific expression of PPARγ in obesity. They also revealed that PPARγ expressed in the intestinal epithelium, and regulates the differentiation and proliferation of this cell-type. They also clarified the significance of PPARγon the development of colon cancer and Crohn's disease and the relationship between overnutrition and these diseases.
We invited Dr. Auwerx in the winter meeting of Japan atherosclerotic society. Japan and France groups presented above results in the meeting. In conclsion, we progressed the studies on molecular mechanisms of diseases caused by ovemutrition by international collraboration. Less