Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue
Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue
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DOI：
10.1038/oby.2008.207
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发表时间：
2008-06-01
期刊：
影响因子：
6.9
通讯作者：
Hermanowski-Vosatka, Anne
中科院分区：
文献类型：
--
作者：
Lee, Mi-Jeong;Fried, Susan K.;Hermanowski-Vosatka, Anne
目的：本研究的主要目的是比较人体大网膜和腹部皮下脂肪组织中皮质醇生成的调节。方法和步骤：手术获取大范围BMI受试者的大网膜和腹部皮下脂肪组织。结果：HSD(HSD1)mRNA和还原酶活性主要表达于脂肪细胞内，且与脂肪细胞大小密切相关。Om的HSD1表达和还原酶活性无明显差异，而皮质醇失活和HSD2mRNA表达(在间质细胞中表达)较高，提示Om的皮质醇周转较高。用胰岛素培养可降低两个库中HSD还原酶的活性。与单独使用胰岛素相比，地塞米松加胰岛素培养只在Om库中增加了HSD还原酶的活性。这种仓库特有的还原酶活性的增加不能用HSD1mRNA或蛋白质的变化来解释，HSD1mRNA或蛋白质的变化是自相矛盾的。然而，仅在Om中，地塞米松和胰岛素联合培养时，己糖-6-磷酸脱氢酶(H6PDH)的mRNA水平比单独使用胰岛素时增加，这表明内质网(ER)内产生更高的烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NADPH)导致更高的HSD还原酶活性。讨论：我们得出结论：在存在胰岛素的情况下，糖皮质激素导致Om脂肪组织中皮质醇活性的特异性增加，这一机制可能有助于脂肪细胞肥大和内脏肥胖。
Objective: Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue.Methods and Procedures: Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity (H-3-cortisone and H-3-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone.Results: Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity.Discussion: We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity.