PDF(Pubmed)
Abstract：
The similarity of the clinical picture of metabolic syndrome and hypercortisolemia supports the hypothesis that obesity may be associated with impaired expression of genes related to cortisol action and metabolism in adipose tissue. The expression of genes encoding the glucocorticoid receptor alpha (GR), cortisol metabolizing enzymes (HSD11B1, HSD11B2, H6PDH), and adipokines, as well as selected microRNAs, was measured by real-time PCR in adipose tissue from 75 patients with obesity, 19 patients following metabolic surgery, and 25 normal-weight subjects. Cortisol levels were analyzed by LC-MS/MS in 30 pairs of tissues. The mRNA levels of all genes studied were significantly (p < 0.05) decreased in the visceral adipose tissue (VAT) of patients with obesity and normalized by weight loss. In the subcutaneous adipose tissue (SAT), GR and HSD11B2 were affected by this phenomenon. Negative correlations were observed between the mRNA levels of the investigated genes and selected miRNAs (hsa-miR-142-3p, hsa-miR-561, and hsa-miR-579). However, the observed changes did not translate into differences in tissue cortisol concentrations, although levels of this hormone in the SAT of patients with obesity correlated negatively with mRNA levels for adiponectin. In conclusion, although the expression of genes related to cortisol action and metabolism in adipose tissue is altered in obesity and miRNAs may be involved in this process, these changes do not affect tissue cortisol concentrations.
摘要：
代谢综合征和高皮质醇血症的临床表现的相似性支持以下假设：肥胖可能与脂肪组织中皮质醇作用和代谢相关基因的表达受损有关。编码糖皮质激素受体α（GR）的基因的表达，皮质醇代谢酶（HSD11B1，HSD11B2，H6PDH），和脂肪因子，以及选定的microRNA，通过实时PCR检测75例肥胖患者的脂肪组织，19例代谢手术后，和25名体重正常的受试者。通过LC-MS/MS分析30对组织中的皮质醇水平。在肥胖患者的内脏脂肪组织（VAT）中，所有研究基因的mRNA水平均显着（p<0.05）降低，并因体重减轻而恢复正常。在皮下脂肪组织（SAT），GR和HSD11B2受此现象的影响。在所研究基因的mRNA水平和选定的miRNA之间观察到负相关（hsa-miR-142-3p，hsa-miR-561和hsa-miR-579)。然而,观察到的变化并没有转化为组织皮质醇浓度的差异，尽管肥胖患者SAT中这种激素的水平与脂联素的mRNA水平呈负相关。总之,尽管脂肪组织中皮质醇作用和代谢相关基因的表达在肥胖中发生了改变，miRNAs可能参与了这一过程，这些变化不影响组织皮质醇浓度。
