Regulation of 11β-HSD genes in human adipose tissue:: Influence of central obesity and weight loss

Objectives: The activity of adipose 11beta-hydroxysteroid dehydrogenase (11beta-HSD)1 is increased in obese subjects, and animal data suggest that increased cortisol formation in adipose tissue contributes to the development of the metabolic syndrome. The aim of this study was to determine whether up-regulation of human adipose 11beta-HSD1 in obesity can also be found at the gene expression level. Research Methods and Procedures: 11beta-HSD gene expression in subcutaneous adipose tissue biopsies of 70 post-menopausal women was studied by real-time reverse-transcription polymerase chain reaction. The influence of weight reduction and in vitro effects of several modulators of adipocyte gene expression on 11beta-HSD genes in human adipocytes were also studied. Results: The 11beta-HSD1 gene was highly expressed in human adipose tissue. 11beta-HSD2 mRNA was also detectable at lower levels. Adipose 11beta-HSD1 gene expression was increased by two-fold and was positively correlated with waist circumference and homeostasis model assessment index of insulin resistance. 11beta-HSD2 gene expression was reduced by half in obese women. Weight reduction did not change gene expression levels of 110-HSD1 or 110-HSD2. Cortisol increased 11beta-HSD1 gene expression in isolated human adipocytes in vitro, whereas estrsadiol, triiodothyronine, angiotensin II, and pioglitazone had no influence. Discussion: Our data suggest that increased expression of the 11beta-HSD1 gene is associated with methabolic abnormalities in obese women and that increased expression of this gene may contribute to the previously reported increased local conversion of cortisol in adipose tissue of obese individuals.