Aim: 

Recent data suggest that Angiotensin II receptor type 1 (AT1) antagonists besides lowering blood pressure reduce obesity-related metabolic disturbances. In order to verify the possible insulin-sensitizing effects of AT1 receptor blockade in adipose tissue we treated male Wistar Kyoto rats with Candesartan cilexetil (Cc; 10 mg/kg/day) for 18 weeks.

Methods: 

Adipocyte cell size was determined by light microscopy after colagenase digestion of adipose tissue. Circulated levels of hormones in serum were determined by RIA. Gene expression of adipokines and RAS components in adipose tissue were evaluated by real-time PCR. AT1 and AT2 receptor protein levels were determined by immunoblot.

Results: 

Significant loss in body weight without change in food intake was observed at the end of the experiment. In epididymal and retroperitoneal adipose tissue significant decrease in mass was noticed due to hypotrophy. Serum leptin was decreased and serum adiponectin was increased in treated rats. Cc lowered leptin and TNFa expression and elevated adiponectin, fatty acid synthase and PPARg mRNA. In addition, Cc treatment resulted in the increase of epididymal AT2 receptor gene and protein expression.

Conclusion: 

We propose that Cc modulates adipokines production and release and regulates fat tissue cellularity. These effects might be the consequence of local AT1 receptor inhibition and/or AT2 receptor stimulation, probably involving PPARg activation. Increased adiponectin and PPARg together with decreased TNFa suggest insulin-sensitising action of long-lasting AT1 receptor blockade. Supported by DIRP, NIMH and by VEGA 2/5090/25.