FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2.1

Title of the proposal

Searching for the role of local renin –angiotensin system in adipose tissue

Institute

Slovak Academy of Sciences, Institute of Experimental Endocrinology
Vlarska 3, 833 06 Bratislava, Slovak Republic

Contact

Research subject for a potential FP6 project

Adipocytes besides representing an important energy store, also synthesize and secrete a number of cardiovascular system affecting substances such as the components of renin – angiotensin system (RAS) (angiotensinogen, renin, ACE and angiotensins), PAI-1, adipsin, leptin, ANP, endothelin, resistin and TNF-a. In addition, the receptors for some of these substances have been identified in adipose tissue.
It is assumed that adipocyte originated angiotensinogen and angiotensin II contribute to activity of circulating RAS. Increased mass of adipose tissue in obesity might produce more angio-tensinogen and angiotensin peptides creating so a direct link between obesity and cardiovascular diseases. On the other hand, angiotensin II receptors in adipose tissue bind circulating as well as locally produced hormone. Under culture conditions angiotensin II inhibits differentiation of preadipocytes. In vivo, angiotensin II receptors of AT₁ subtype are downregulated in obesity. Besides adipocytes, AT₁ receptors were found also in fat tissue vasculature. These receptors might regulate local blood flow in adipose tissue.
In order to elucidate the function of local RAS in fat tissue we will study the components of this system in different animal models of obesity and under pharmacological blockade. Special attention will be paid to changes of angiotensin II receptor expression in adipocytes and stromal vascular fraction of fat tissue. The association of adipose tissue RAS activity with nitric oxide production and PAI-1 expression is planned to study as well. In addition, the link between RAS in adipocytes and their metabolic activity will be studied with focus on the role of adipose tissue in development of insulin resistance.

Recent international cooperation of the research team

1/ Institute of Pharmacology and Experimental Medicine, University of L. Pasteur, Strasbourg, France
2/ National Institute of Menthal Health, Bethesda, USA
3/ Institute of Molecular Genetics, Prague, Czech Republic

Proposer´s relevant publications related to the research subject

Zorad S., Fickova M., Zelezna B., Macho L., Kral JG: The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. Gen Physiol Biophys 1995, 14, 383-391
Pinterova L., Krizanova O., Zorad S: Rat epididymal fat tissue express all components of the renin-angiotensin system. Gen Physiol Biophys 2000, 19, 329-334
Pinterova L., Zelezna B., Fickova M., Macho L., Krizanova O., Jezova D., Zorad S: Elevated receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity. Horm Metab Res 2001, 33, 708-712