Endocrinology and Genomics, Laval University Medical Center, Canada.
J Steroid Biochem Mol Biol. 2010 Oct;122(1-3):28-34. doi: 10.1016/j.jsbmb.2010.02.024. Epub 2010 Mar 3.
Adipose tissue glucocorticoid action relies on local enzymatic interconversion and glucocorticoid receptor (GR) availability. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), 2 (11β-HSD2) and hexose-6-phosphate dehydrogenase (H6PDH) are likely involved in glucocorticoid activation/inactivation within adipose tissue. We examined adipose tissue mRNA expression of genes related to glucocorticoid action and their association with total and visceral adiposity. Messenger RNA was measured in paired subcutaneous and omental fat samples obtained from 56 women (age: 47.3 ± 4.8 years, BMI: 27.1 ± 5.2 kg/m(2)) undergoing gynaecological surgery. Expression levels of 11β-HSD2, H6PDH and GRα were higher in omental adipose tissue while 11β-HSD1 expression was similar between fat compartments. Subcutaneous and omental 11β-HSD1 mRNA abundances were positively associated with total and visceral adiposity whereas omental H6PDH mRNA abundance was negatively associated with these measures. Only omental 11β-HSD1 mRNA expression remained significantly associated with visceral adipose tissue area following statistical adjustment for fat mass, age and menopausal status. Omental 11β-HSD1 mRNA expression explained 19.1% of the variance in visceral adipose tissue area. Omental fat tissue 11β-HSD-1 protein and cortisol levels were higher in visceral obese women, supporting findings obtained with 11β-HSD-1 mRNA. These results suggest that among the transcripts examined only omental 11β-HSD1 is independently associated with visceral obesity in women.
脂肪组织糖皮质激素的作用依赖于局部酶的相互转化和糖皮质激素受体(GR)的可利用性。11β-羟类固醇脱氢酶 1 型(11β-HSD1)、2 型(11β-HSD2)和己糖-6-磷酸脱氢酶(H6PDH)可能参与了脂肪组织中糖皮质激素的激活/失活。我们研究了与糖皮质激素作用相关的基因在脂肪组织中的 mRNA 表达及其与总体和内脏肥胖的关系。在接受妇科手术的 56 名女性(年龄:47.3 ± 4.8 岁,BMI:27.1 ± 5.2 kg/m²)的皮下和网膜脂肪样本中测量了信使 RNA。网膜脂肪组织中 11β-HSD2、H6PDH 和 GRα 的表达水平较高,而脂肪隔室之间的 11β-HSD1 表达水平相似。皮下和网膜 11β-HSD1 mRNA 丰度与总体和内脏肥胖呈正相关,而网膜 H6PDH mRNA 丰度与这些指标呈负相关。在对脂肪量、年龄和绝经状态进行统计调整后,只有网膜 11β-HSD1 mRNA 表达与内脏脂肪组织面积仍呈显著相关。网膜 11β-HSD1 mRNA 表达解释了内脏脂肪组织面积变异的 19.1%。内脏肥胖女性网膜脂肪组织 11β-HSD-1 蛋白和皮质醇水平较高,支持了 11β-HSD-1 mRNA 的研究结果。这些结果表明,在所检查的转录本中,只有网膜 11β-HSD1 与女性内脏肥胖独立相关。