Service of Endocrinology, Hospital Carlos III, Sinesio Delgado 10, Madrid, 28029, Spain.
Obes Surg. 2012 Mar;22(3):478-86. doi: 10.1007/s11695-011-0524-9.
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).
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.
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.
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.
肝脏 11β-羟甾类脱氢酶 1（11β-HSD1）活性可将皮质酮（无活性）转化为皮质醇，在肥胖中受到下调。然而，在伴有代谢异常（如糖尿病）的肥胖患者中，这种代偿机制会失效。为了进一步描述肥胖中组织特异性皮质醇再生，我们研究了与局部皮质醇生成相关的基因的 mRNA 表达，即 11β-HSD1、己糖-6-磷酸脱氢酶（H6PDH）和皮质醇作用、糖皮质激素受体（GR）以及磷酸烯醇丙酮酸羧激酶（PEPCK）在肝脏中，以及内脏（VAT）和皮下（SAT）脂肪组织中，来自患有和不患有代谢综合征（MS）的病态肥胖患者。
50 名接受减肥手术的病态肥胖患者，14 名男性（平均年龄，41.3±3.5 岁；BMI，48.0±3.6 kg/m²）和 36 名女性（平均年龄，44.6±1.9 岁；BMI，44.9±1.2 kg/m²），被分为有 MS（MS+，n=20）或无 MS（MS-，n=30）。通过实时聚合酶链反应测量组织 mRNA 水平。
MS 肥胖患者肝内这些基因的 mRNA 水平更高（11β-HSD1，P=0.002；H6PDH，P=0.043；GR，P=0.033；PEPCK，P=0.032），且与定义 MS 的临床特征数量呈正相关。这四个基因的表达彼此之间呈正相关。与肝脏相反，当比较 MS+和 MS-肥胖患者时，这些基因在 VAT 或 SAT 中没有差异表达。
参与局部皮质醇再生和作用的基因在肝脏中的协同上调支持了局部肝高皮质醇血症导致病态肥胖患者 MS 发展的概念。
