The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) amplifies intracellular glucocorticoid action in vivo. 11beta-HSD-1 activity is increased in adipose tissues of obese humans and genetically obese rodents, providing a mechanistic basis for the similarities between metabolic disease arising from high circulating glucocorticoids (Cushing's syndrome) and idiopathic obesity/metabolic syndrome where plasma glucocorticoids are typically unaltered. Fat-specific overexpression of 11beta-HSD-1 produces a metabolic syndrome in mice, whereas 11beta-HSD-1 null mice resist high-fat diet (HF)-induced visceral obesity and its metabolic consequences. Here we compared the effects of chronic (18 wk) HF feeding on adipose 11beta-HSD-1 activity in strains of mice that are either resistant (A/J) or prone (C57BL/6J) to metabolic disease. 11beta-HSD-1 activity was highest in sc fat, followed by epididymal fat, with lowest activity in the mesenteric visceral depot of both strains. 11beta-HSD-1 activity was lower in white adipose tissues of AM compared with C57BL/6J mice. Chronic HF feeding unexpectedly caused a down-regulation of 11beta-HSD-1 in adipose tissues of both strains, despite comparable adiposity. However, AM mice down-regulated adipose 11beta-HSD-1 to a significantly lower level than C57BL/6J mice in white and thermogenic brown adipose tissues. We propose that a lower adipose 11beta-HSD-1 set point affords a metabolic protection to AM mice. Adaptive down-regulation of adipose 11beta-HSD-1 in response to chronic HF represents a novel mechanism that may counteract metabolic disease.
|Number of pages||6|
|Publication status||Published - Jun 2004|