Liver Upregulation of Genes Involved in Cortisol Production and Action Is Associated with Metabolic Syndrome in Morbidly Obese Patients
Liver Upregulation of Genes Involved in Cortisol Production and Action Is Associated with Metabolic Syndrome in Morbidly Obese Patients
复制标题
肝脏上调参与皮质醇产生和作用的基因与病态肥胖患者的代谢综合征相关
作者：
E. Torrecilla;G. Fernández;D. Vicent;F. Sánchez‐Franco;A. Barabash;L. Cabrerizo;A. Sánchez;A. Torres;M. Rubio
研究背景肝脏11-羟基类固醇脱氢酶1(11β-β-HSD1)活性在肥胖症中表达下调，其作用是将皮质醇(非活性)转化为皮质醇。然而，这种补偿在患有代谢异常的肥胖者身上失败了，比如糖尿病。为了进一步研究肥胖时组织特异性皮质醇的再生，我们研究了与局部皮质醇产生相关的基因，即11β-hsd1，己糖-6-磷酸脱氢酶(H6PDH)和皮质醇作用基因，肝脏中糖皮质激素受体(GR)和皮质醇靶基因磷酸烯醇式丙酮酸羧激酶(PEPCK)，以及内脏和皮下脂肪组织中代谢综合征(MS)患者的内脏和皮下脂肪组织。体重指数48.0 ± 3.6 kg/m2)和36例女性(平均年龄44.6 ± 1.9岁；体重指数44.9 ± 1.2 kg/m2)，分为MS(MS+，n = 20)和无MS(MS−，n = 30)。结果肥胖MS患者(11β-HSD1，P = 0.002；H6PDH，P = 0.043；GR，P = 0.033；PEPCK，P = 0.032)肝组织中这些基因的表达水平均较高，且与MS的临床特征呈正相关。与肝脏相比，当MS+和MS−肥胖患者进行比较时，这些基因在VAT或SAT中的表达没有差异。结论局部皮质醇再生和作用涉及的基因在肝脏中的协同上调支持了局部肝脏皮质醇增多症与病态肥胖患者MS的发生有关的概念。
BackgroundHepatic 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).MethodsFifty morbidly obese patients undergoing bariatric surgery, 14 men (mean age, 41.3 ± 3.5 years; BMI, 48.0 ± 3.6 kg/m2) and 36 women (mean age, 44.6 ± 1.9 years; BMI, 44.9 ± 1.2 kg/m2), were classified as having MS (MS+, n = 20) or not (MS−, n = 30). Tissue mRNA levels were measured by real-time polymerase chain reaction.ResultsHepatic 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.ConclusionsCoordinated 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.
影响因子：
7.7
作者：
Liu, YJ;Nakagawa, Y;Friedman, TC
通讯作者：
Friedman, TC