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

Int J Obes (Lond). 2009 Apr;33(4):473-80. doi: 10.1038/ijo.2009.4. Epub 2009 Feb 10.


Objective: 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.

Design: 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.

Result: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases / genetics*
  • Adult
  • Body Mass Index
  • Circadian Rhythm / physiology*
  • Female
  • Gene Expression
  • Humans
  • Hydrocortisone / metabolism*
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged
  • PPAR gamma / genetics*
  • Polymerase Chain Reaction
  • Subcutaneous Fat / metabolism*


  • PPAR gamma
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Hydrocortisone