Endocrine Abstracts

The metabolism of glucocorticoids within adipose tissue, by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), is known to be altered in obesity and following high fat feeding. Until recently, little attention has been paid to the fat depots found directly adjacent to blood vessels. Emerging evidence suggests that perivascular adipose may play a key role in modulating vascular function. The presence of steroidogenic enzymes within perivascular adipose, and the effect of obesity and high fat feeding on enzyme activity have not been previously explored. We hypothesized that 11HSD1 mRNA and activity is present in rodent peri-aortic adipose, and that this enzyme is enhanced by obesity, and reduced by high fat feeding. Peri-aortic adipose tissue was obtained from male C57B6J mice following 8 weeks of high fat or chow diet, and lean and obese Zucker rats. 11HSD1 enzyme activity was determined in homogenized tissue in vitro by conversion of tritiated corticosterone to 11-dehydrocorticosterone. mRNA for 11HSD1, 5alpha-reductase and glucocorticoid receptor (GR) in peri-aortic adipose from lean and obese Zucker rats was quantified by real time PCR and corrected for cyclophillin and 18S. Data are mean plus/minus SEM. 11HSD1 activity was detected in murine peri-aortic adipose (56±7% conversion after 2hrs) and was significantly reduced following high fat feeding (25±2% conversion, n=6, P<0.001). There was an increase in 11HSD1 activity (20±2% conversion after 4hrs vs 14±1% conversion in controls, n=8, P=0.05) and expression (1.1±0.2 vs 0.6±0.1, n=8, P<0.005) in peri-aortic adipose from obese Zucker rats. In addition, obesity was associated with a reduction in 5α-reductase (0.7±0.1 vs 1.0±0.1 in controls, n=8, P<0.05) and an elevation in GR (1.0±0.1 cf 0.7±0.1, n=8, P<0.01) mRNA. These data demonstrate that perivascular adipose is a novel site of glucocorticoid metabolism. Altered glucocorticoid metabolism within adipose at this location may contribute to vascular dysfunction in obesity.