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  • Title: Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects.
    Author: Alberti L, Girola A, Gilardini L, Conti A, Cattaldo S, Micheletto G, Invitti C.
    Journal: Int J Obes (Lond); 2007 Dec; 31(12):1826-31. PubMed ID: 17593901.
    Abstract:
    OBJECTIVE: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor alpha (TNFalpha) and two glucocorticoid-regulated adipokines able to influence the metabolic control. DESIGN AND SUBJECTS: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1+/-5.3 kg/m(2)). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9+/-5.1 kg/m(2)). MEASUREMENTS: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFalpha and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11beta-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFalpha. Western blot analysis to evaluate 11beta-HSD1 protein expression. RESULTS: In the majority of the obese subjects, VAT expresses more 11beta-HSD1 than SAT. VAT 11beta-HSD1 expression was not associated with metabolic disorders. SAT 11beta-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11beta-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11beta-HSD1 was associated with increased adiponectin and TNFalpha expression and decreased serum adiponectin levels (all P's <0.05). CONCLUSIONS: In obese subjects, increased 11beta-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.
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