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Liver upregulation of genes involved in cortisol production and action is associated with metabolic syndrome in morbidly obese patients.
- Source :
-
Obesity surgery [Obes Surg] 2012 Mar; Vol. 22 (3), pp. 478-86. - Publication Year :
- 2012
-
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).<br />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.<br />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.<br />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.
- Subjects :
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics
Adipose Tissue enzymology
Adult
Bariatric Surgery
Cortisone metabolism
Female
Gene Expression Regulation
Humans
Hydrocortisone biosynthesis
Hydrocortisone genetics
Male
Metabolic Syndrome genetics
Obesity, Morbid genetics
Obesity, Morbid surgery
Phosphoenolpyruvate Carboxykinase (ATP) genetics
RNA, Messenger
Real-Time Polymerase Chain Reaction
Up-Regulation
11-beta-Hydroxysteroid Dehydrogenase Type 1 metabolism
Hydrocortisone metabolism
Liver enzymology
Metabolic Syndrome enzymology
Obesity, Morbid enzymology
Phosphoenolpyruvate Carboxykinase (ATP) metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1708-0428
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Obesity surgery
- Publication Type :
- Academic Journal
- Accession number :
- 21964795
- Full Text :
- https://doi.org/10.1007/s11695-011-0524-9