Proceedings of the 14th Novo Nordisk Symposium on Growth Hormone and Endocrinology, Estoril/Lisbon, March 28-29, 2003 and Proceedings of the SGA Satellite Symposium, Estoril/Lisbon, March 27, 2003. Editors: M.B. Ranke, Tübingen; J.S. Christiansen, Aarhus

The Adipocyte as an Endocrine Organ

Importance of Adipocytokines in Obesity-Related Diseases
Yuji Matsuzawa^a,b, Iichiro Shimomura^a, Shinji Kihara^a, Tohru Funahashi<sup>a

a</sup>Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, and
^bSumitomo Hospital, Osaka,Japan

Address of Corresponding Author

Horm Res 2003;60 (Suppl. 3):56-59 (DOI: 10.1159/000074502)

  Key Words

• Adiponectin
• Visceral fat
• Insulin resistance

  Abstract

To elucidate the biological characteristics of adipose tissue, we analyzed the gene expression profile of visceral and subcutaneous fat. Unexpectedly, adipose tissue, especially visceral fat, expressed a variety of genes for secretory proteins. About 30% of the genes expressed in visceral adipose tissue encoded secretory proteins and most were biologically active molecules, which we called adipocytokines. We found plasminogen activator inhibitor type 1 and heparin binding EGF-like growth factor. Production of these atherogenic adipocytokines was shown to increase with the accumulation of visceral fat, which may be one of the mechanisms of vascular disease in visceral obesity. We found a unique and novel collagen-like protein, adiponectin, encoded by the most abundantly expressed gene in adipose tissue, termed apM1 (adipose most abundant gene transcript-1). Plasma levels of adiponectin ranged from 0.3 to approximately 3 mg/dl but were decreased in patients with visceral obesity, type 2 diabetes and coronary artery disease (CAD). Screening for mutations in the adiponectin gene revealed that patients carrying a missense mutation showed markedly decreased plasma levels of adiponectin and had CAD. These data suggest that hypoadiponectinemia may be considered an important risk factor for CAD. Cell biology studies revealed that adiponectin has a potent inhibitory effect on the expression of adhesion molecules in endothelial cells and an inhibitory effect on the expression in macrophages. In order to confirm these antidiabetic and antiatherogenic functions of adiponectin, we developed adiponectin knockout mice. Adiponectin knockout mice showed severe insulin resistance and impaired glucose metabolism when fed a high-fat, high-sucrose diet. Knockout mice also developed intimal thickening in response to endothelial injury.

Copyright © 2003 S. Karger AG, Basel

  Author Contacts

Prof. Yuji Matsuzawa
Sumitomo Hospital
5-3-20 Nakanoshima, Kita-ku
Osaka 530-0005 (Japan)
Tel. +81 6 6443 1261, Fax +81 6 6444 3975, E-Mail matsuzawa-yuji@sumitomo-hp.or.jp

  Article Information

Number of Print Pages : 4
Number of Figures : 0, Number of Tables : 0, Number of References : 16