Regulation of 11β-HSD genes in human adipose tissue:: Influence of central obesity and weight loss
Regulation of 11β-HSD genes in human adipose tissue:: Influence of central obesity and weight loss
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DOI：
10.1038/oby.2004.3
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Sharma, AM
中科院分区：
文献类型：
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作者：
Engeli, S;Böhnke, J;Sharma, AM
目的：脂肪11 β-羟基类固醇脱氢酶（11 β-HSD）1的活性在肥胖受试者中增加，动物数据表明脂肪组织中皮质醇形成的增加有助于代谢综合征的发展。本研究的目的是确定是否上调人类脂肪11 β-HSD 1在肥胖症中也可以发现在基因表达水平。研究方法和程序：11 β-HSD基因表达在皮下脂肪组织活检70绝经后妇女进行了研究，通过实时逆转录聚合酶链反应。结果：11 β-HSD 1基因在人脂肪组织中高表达。11 β-HSD 2 mRNA在较低水平也可检测到。脂肪11 β-HSD 1基因表达增加2倍，并与腰围和胰岛素抵抗稳态模型评估指数呈正相关。11 β-HSD 2基因表达在肥胖女性中减少了一半。体重减轻并没有改变110-HSD 1或110-HSD 2的基因表达水平。皮质醇增加了体外分离的人脂肪细胞中11 β-HSD 1基因的表达，而雌二醇、三碘甲状腺原氨酸、血管紧张素II和吡格列酮则没有影响。我们的数据表明，11 β-HSD 1基因与肥胖妇女的代谢异常有关，该基因表达的增加可能导致先前报道的肥胖妇女脂肪组织中皮质醇的局部转化增加。肥胖的人
Objectives: The activity of adipose 11beta-hydroxysteroid dehydrogenase (11beta-HSD)1 is increased in obese subjects, and animal data suggest that increased cortisol formation in adipose tissue contributes to the development of the metabolic syndrome. The aim of this study was to determine whether up-regulation of human adipose 11beta-HSD1 in obesity can also be found at the gene expression level.Research Methods and Procedures: 11beta-HSD gene expression in subcutaneous adipose tissue biopsies of 70 post-menopausal women was studied by real-time reverse-transcription polymerase chain reaction. The influence of weight reduction and in vitro effects of several modulators of adipocyte gene expression on 11beta-HSD genes in human adipocytes were also studied.Results: The 11beta-HSD1 gene was highly expressed in human adipose tissue. 11beta-HSD2 mRNA was also detectable at lower levels. Adipose 11beta-HSD1 gene expression was increased by two-fold and was positively correlated with waist circumference and homeostasis model assessment index of insulin resistance. 11beta-HSD2 gene expression was reduced by half in obese women. Weight reduction did not change gene expression levels of 110-HSD1 or 110-HSD2. Cortisol increased 11beta-HSD1 gene expression in isolated human adipocytes in vitro, whereas estrsadiol, triiodothyronine, angiotensin II, and pioglitazone had no influence.Discussion: Our data suggest that increased expression of the 11beta-HSD1 gene is associated with methabolic abnormalities in obese women and that increased expression of this gene may contribute to the previously reported increased local conversion of cortisol in adipose tissue of obese individuals.