The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

Journal Article · Sat Jul 01 04:00:00 EDT 2006 · Journal of Biomedicine and Biotechnology

OSTI ID:931949

Kim, Suyeon ^[1]; Soltani-Bejnood, Morvarid ^[1]; Quignard-Boulange, Annie ^[2]; Massiera, Florence ^[3]; Teboul, Michele ^[3]; Ailhaud, Gerard ^[3]; Kim, Jung ^[1]; Moustaid-Moussa, Naima ^[1]; Voy, Brynn H ^[4]

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1. University of Tennessee, Knoxville (UTK)
2. Centre Biomedical des Cordeliers, Paris, France
3. Centre de Biochimie, Nice, France
4. ORNL

BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

• Research Organization: Oak Ridge National Laboratory (ORNL)
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 931949
• Journal Information: Journal of Biomedicine and Biotechnology, Journal Name: Journal of Biomedicine and Biotechnology Vol. 2006
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ADIPOSE TISSUE
ANGIOTENSIN
Angiotensinogen
BLOOD PRESSURE
Hypertension
INSULIN
METABOLIC DISEASES
MICE
Obesity
RENIN
SENSITIVITY
transgenic. knockout