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

Abstract

Objective:

To analyze, in morbid obese patients, the expression of several human genes regulating cortisol metabolism, such as glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), stearoyl-acute regulatory protein (StAR), 5α-reductase type I (5α-R) and peroxisome proliferator-activated receptor-γ (PPARγ) 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 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, 11βHSD1 and PPARγ genes were highly expressed in both subcutaneous and visceral depots. StAR and 5α-R genes were detected at lower levels. The expression of 11βHSD2 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 5α-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.

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Acknowledgements

We thank P Gomez-Abellan for her contributions and support in AT culture development. We also thank Dr J Lujan for his technical assistance in obtaining adipose tissue.

This work was supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG) and by the Government of Education, Science and Research of Murcia (project BIO/FFA 07/01-0004).

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Correspondence to M Garaulet.

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Hernandez-Morante, J., Gomez-Santos, C., Milagro, F. et al. Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue. Int J Obes 33, 473–480 (2009). https://doi.org/10.1038/ijo.2009.4

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