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Liver Upregulation of Genes Involved in Cortisol Production and Action Is Associated with Metabolic Syndrome in Morbidly Obese Patients

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Abstract

Background

Hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, which converts cortisone (inactive) to cortisol, is downregulated in obesity. However, this compensation fails in obese with metabolic abnormalities, such as diabetes. To further characterize the tissue-specific cortisol regeneration in obesity, we have investigated the mRNA expression of genes related to local cortisol production, i.e., 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PDH) and cortisol action, glucocorticoid receptor (GR) and a cortisol target gene, phosphoenolpyruvate carboxykinase (PEPCK) in the liver, and visceral (VAT) and subcutaneous (SAT) adipose tissues from morbidly obese patients with and without metabolic syndrome (MS).

Methods

Fifty morbidly obese patients undergoing bariatric surgery, 14 men (mean age, 41.3 ± 3.5 years; BMI, 48.0 ± 3.6 kg/m2) and 36 women (mean age, 44.6 ± 1.9 years; BMI, 44.9 ± 1.2 kg/m2), were classified as having MS (MS+, n = 20) or not (MS−, n = 30). Tissue mRNA levels were measured by real-time polymerase chain reaction.

Results

Hepatic mRNA levels of these genes were higher in obese patients with MS (11β-HSD1, P = 0.002; H6PDH, P = 0.043; GR, P = 0.033; PEPCK, P = 0.032) and positively correlated with the number of clinical characteristics that define the MS. The expression of the four genes positively correlated among them. In contrast to the liver, these genes were not differently expressed in VAT or SAT, when MS+ and MS− obese patients were compared.

Conclusions

Coordinated liver-specific upregulation of genes involved in local cortisol regeneration and action support the concept that local hepatic hypercortisolism contributes to development of MS in morbidly obese patients.

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Acknowledgments

The authors thank Rocío González González and Marina Pollán Santamaría for their excellent statistical assistance. This work was supported by Research Grants FMM 07 (to M.A.R.) and FMM 11 (to G.F.V.) from the Mutua Madrileña Foundation (Madrid, Spain) and by a 2009 award from Sendimad. E.T.G. is a Post-doctoral Fellow supported by the Mutua Madrileña Foundation.

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Authors and Affiliations

  1. Service of Endocrinology, Hospital Carlos III, Sinesio Delgado 10, Madrid, 28029, Spain

    Esther Torrecilla, Gumersindo Fernández-Vázquez, David Vicent & Franco Sánchez-Franco

  2. Service of Endocrinology, Facultad de Medicina, Universidad Complutense, Hospital Clínico Universitario San Carlos, Madrid, 28040, Spain

    Ana Barabash, Lucio Cabrerizo & Miguel Ángel Rubio

  3. Department of General Surgery 2, Facultad de Medicina, Universidad Complutense, Hospital Clínico Universitario San Carlos, Madrid, 28040, Spain

    Andrés Sánchez-Pernaute & Antonio J. Torres

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  1. Esther Torrecilla
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Correspondence to Gumersindo Fernández-Vázquez.

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Torrecilla, E., Fernández-Vázquez, G., Vicent, D. et al. Liver Upregulation of Genes Involved in Cortisol Production and Action Is Associated with Metabolic Syndrome in Morbidly Obese Patients. OBES SURG 22, 478–486 (2012). https://doi.org/10.1007/s11695-011-0524-9

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  • DOI: https://doi.org/10.1007/s11695-011-0524-9

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