title: Liver upregulation of genes involved in cortisol production and action is associated with metabolic syndrome in morbidly obese patients.
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/m(2)) and 36 women (mean age, 44.6 ± 1.9 years; BMI, 44.9 ± 1.2 kg/m(2)), 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.
authors.affiliation: Service of Endocrinology, Hospital Carlos III, Sinesio Delgado 10, Madrid, 28029, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Torrecilla
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fernández-Vázquez
authors.forename: David
authors.initials: D
authors.lastname: Vicent
authors.forename: Franco
authors.initials: F
authors.lastname: Sánchez-Franco
authors.forename: Ana
authors.initials: A
authors.lastname: Barabash
authors.forename: Lucio
authors.initials: L
authors.lastname: Cabrerizo
authors.forename: Andrés
authors.initials: A
authors.lastname: Sánchez-Pernaute
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Torres
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rubio
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology; D000328:Adult; D050110:Bariatric Surgery; D003348:Cortisone / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology* / Q000235:genetics; D009767:Obesity, Morbid / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D003348:Cortisone; D006854:Hydrocortisone