Alberti L, Girola A, Gilardini L, Conti A, Cattaldo S, Micheletto G, Invitti C
Unit for Metabolic Diseases and Diabetes, Istituto Auxologico Italiano, Milan, Italy.
Int J Obes (Lond). 2007 Dec;31(12):1826-31. doi: 10.1038/sj.ijo.0803677. Epub 2007 Jun 26.
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.
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)).
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.
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).
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.
脂肪组织中糖皮质激素生成在人类代谢紊乱发展过程中的作用尚未完全明确。我们研究了在肥胖受试者中，皮下（SAT）和内脏（VAT）脂肪组织中11β-羟基类固醇脱氢酶1型（11β-HSD1）的表达是否与代谢紊乱的发生、脂联素和肿瘤坏死因子α（TNFα）的表达以及两种能够影响代谢控制的糖皮质激素调节的脂肪因子相关。
62名肥胖患者参与了本研究。SAT和VAT样本取自13名接受减肥手术的患者（体重指数（BMI）39.1±5.3kg/m²）。SAT样本取自49名接受脐周活检的患者（BMI 36.9±5.1kg/m²）。
对无已知糖尿病的受试者进行口服葡萄糖耐量试验。检测循环中的葡萄糖、脂质、胰岛素、脂联素、TNFα以及尿游离皮质醇水平。采用实时定量PCR法测定11β-HSD1、6-磷酸己糖脱氢酶（H6PDH）、脂联素和TNFα的mRNA水平。通过蛋白质免疫印迹分析评估11β-HSD1蛋白表达。
在大多数肥胖受试者中，VAT中11β-HSD1的表达高于SAT。VAT中11β-HSD1的表达与代谢紊乱无关。与无代谢综合征的受试者相比，有代谢综合征的受试者SAT中11β-HSD1的mRNA水平更高（P<0.05）；与糖耐量受损或正常的患者相比，2型糖尿病患者SAT中11β-HSD1的mRNA水平更高（P<0.0001）。SAT中11β-HSD1的表达与空腹血糖（P<0.0001）和尿游离皮质醇水平（P<0.01）独立相关，11β-HSD1表达增加与脂联素和TNFα表达增加以及血清脂联素水平降低相关（所有P值<0.05）。
在肥胖受试者中，SAT而非VAT中11β-HSD1表达增加与代谢状况恶化相关。我们推测脂肪组织中较高的糖皮质激素生成可能通过减少脂联素释放促进代谢紊乱的发展。
