[Effect of free fatty acids on CYP19A1 (aromatase) gene expression in human adipose tissue stromal vascular fraction cells].

Przeglad lekarski Pub Date : 2016-01-01
Urszula Czech, Wojciech Dudek, Urszula Ciałowicz, Aldona Dembinska-Kiec, Beata Kiec-Wilk
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Abstract

Aromatase plays an important role in the estrogen biosynthesis. Its gen (CYP19A1) is expressed in preadipocytes (stromal vascular fraction, SVF) of adipose tissue. Estrogens are found to be protective for metabolism homeostasis, and cardiovascular system. Disturbed dietary and endogenous fatty acids (FAs) turnover is responsible for development of metabolic syndrome and it complications. Aim of the work was to investigate the effect of physiological concentrations of acids: arachidonic (AA), oleic (OA), palmitynoic (PA) and eikozapentaenoic (EPA) on CYP19A1 expression in differentiating human SVF, able to form adipocytes as well as endothelial cells.

Material and methods: Human (n=38 healthy woman) SVF cells were isolated from subcutaneous adipose tissue harvested intrasurgery. SVF cells were incubated in proadipogenic or angiogenic media to obtain adipocytes (Adipo-SVF) or endothelial (Angio-SVF) cells (confirmed by microarray). Changes in the CYP19A1 expression induced by 24hs incubation in the presence of FAs (10 – 30 μM )were monitored by the Real time PCR (qRT -PCR).

Results: The aromatase gene expression correlated positively with BMI of patients, but only in group of obese or overweight women. The negative correlation was found in the group of young, slim women. The highest expression of aromatase was found in the fresh, not differentiated SVF. In differentiating to endothelial cells (Angio - SVF) OA inhibited (p=0.008), when n-3 polyunsaturated AA activated (p=0.003) the CYP19A1 gene expression. In differentiating to preadipocytes (Adipo-SVF) AA significantly (p=0.031) inhibited CYP19A1 expression.

Conclusion: The changes in the aromatase gene expression in differentiating SVF has been confirmed. The different effect of the dietary FA (OA vs. AA) on the aromatase gene expression argue for the role of the locally formed proangiogenic estrogens.

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游离脂肪酸对人脂肪组织间质血管部分细胞CYP19A1(芳香化酶)基因表达的影响
芳香化酶在雌激素的生物合成中起着重要作用。其原(CYP19A1)在脂肪组织的前脂肪细胞(基质血管部分,SVF)中表达。雌激素被发现对代谢稳态和心血管系统有保护作用。饮食和内源性脂肪酸(FAs)转换紊乱是代谢综合征及其并发症的发生的原因。本研究旨在探讨花生四烯酸(AA)、油酸(OA)、棕榈酸(PA)和二氮二烯酸(EPA)生理浓度对分化成脂肪细胞和内皮细胞的人SVF中CYP19A1表达的影响。材料和方法:从术中收获的皮下脂肪组织中分离人(n=38名健康女性)SVF细胞。svf细胞在前脂肪生成或血管生成培养基中孵育,获得脂肪细胞(Adipo-SVF)或内皮细胞(Angio-SVF)(通过微阵列证实)。采用Real - timePCR (qRT - pcr)检测FAs (10 ~ 30μM)作用24h后cyp19a1表达的变化。结果:芳香化酶基因表达与患者bmi呈正相关,但仅存在于肥胖或超重女性群体中。在年轻苗条的女性群体中发现了负相关。芳香化酶在新鲜未分化的svf中表达最高。在向内皮细胞(血管- SVF)分化时,OA抑制(p=0.008),当n-3多不饱和aa激活(p=0.003) cyp19a1基因表达时。在分化前脂肪细胞(Adipo-SVF)中,AA显著抑制cyp19a1的表达(p=0.031)。结论:芳香化酶基因在svf分化过程中的表达变化已得到证实。膳食FA (OA vs.AA)对芳香化酶基因表达的不同影响证明了局部形成的促血管生成雌激素的作用。
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