代谢功能障碍女性的脂肪组织中雄激素代谢和芳香化作用增强。
Increased Adipose Tissue Indices of Androgen Catabolism and Aromatization in Women With Metabolic Dysfunction.
机构信息
Centre de recherche de l'Institut universitaire de cardiologie et pneumologie de Québec-Université Laval, Québec City, QC G1V 4G5, Canada.
École de nutrition, Université Laval, Québec City, QC G1V 0A6, Canada.
出版信息
J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3330-e3342. doi: 10.1210/clinem/dgac261.
CONTEXT
Body fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue.
OBJECTIVE
Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity.
METHODS
Samples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product over substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR.
RESULTS
VAT aromatase activity was positively associated with VAT adipocyte hypertrophy (P valueadj < 0.01) and negatively with plasma high-density lipoprotein (HDL)-cholesterol (P valueadj < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age, and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity, and higher aromatase expression and activity indices.
CONCLUSION
In women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction.
背景
体脂分布是肥胖相关合并症的一个风险因素，脂肪组织功能障碍在这种关联中起作用。在人类中，体脂分布存在性别差异，类固醇激素已知可调节脂肪组织内的几个细胞过程。
目的
我们的目的是研究在严重肥胖个体中，脂肪组织内类固醇浓度和类固醇生成酶的表达或活性是否与脂肪组织功能障碍的特征相关。
方法
本研究纳入了 40 名减肥手术候选人（31 名女性，9 名男性）。手术过程中采集了内脏（VAT）和皮下脂肪组织（SAT）。采用组织学染色和半自动定量相结合的方法测量脂肪组织形态。提取后，通过液相色谱电喷雾串联质谱法（LC-ESI-MS/MS）测定脂肪组织内和血浆中的类固醇浓度。通过产物与底物的比值来估计芳香酶活性，而通过荧光探针直接测量 AKR1C2 活性。通过定量 PCR 测量基因表达。
结果
VAT 芳香酶活性与 VAT 脂肪细胞肥大呈正相关（调整后 P 值<0.01），与血浆高密度脂蛋白（HDL）-胆固醇呈负相关（调整后 P 值<0.01），而 SAT 芳香酶活性甚至在调整腰围、年龄和激素避孕药使用后，也可预测女性的血脂异常。我们还比较了高和低内脏脂肪指数（VAI）的女性，发现 VAT 过剩的特征是脂肪组织功能障碍，增加的 AKR1C2 活性反映了雄激素的分解代谢增加，以及更高的芳香酶表达和活性指数。
结论
在女性中，增加的雄激素分解代谢或芳香化与内脏肥胖和脂肪组织功能障碍有关。
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