Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

Abstract

To analyze, in morbid obese patients, the expression of several human genes regulating cortisol metabolism, such as glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), stearoyl-acute regulatory protein (StAR), 5alpha-reductase type I (5alpha-R) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in two different adipose depots. A second objective was to characterize the circadian rhythmicity of these genes in both adipose tissue (AT) regions. Visceral and subcutaneous abdominal AT biopsies were obtained from obese patients (body mass index >or=40 kg m(-2)). To carry out rhythmic expression analysis, AT explants were cultured for 24 h and gene expression at times (T) 0, 6, 12 and 18 h, was performed with quantitative real-time PCR. GR, 11betaHSD1 and PPARgamma genes were highly expressed in both subcutaneous and visceral depots. StAR and 5alpha-R genes were detected at lower levels. The expression of 11betaHSD2 was quantified in both AT depots with a higher expression in the visceral depot (P=0.032). Both sexes had similar gene expression levels, except for 5alpha-R (P=0.002). The genes studied showed circadian rhythmicity being more robust in visceral than in subcutaneous AT. Genes ranged in anti-phase between both depots (P=0.002). This rhythmicity was maintained in an AT culture. We have shown for the first time circadian rhythmicity in glucocorticoid-related gene expression in human AT ex vivo. These results may have potential therapeutic implications with respect to the pathogenesis and treatment of diseases, such as obesity, type 2 diabetes and cardiovascular diseases.