单不饱和脂肪酸的新合成调节外泌体介导的人类颗粒细胞脂质输出。

IF 3.8 3区 医学 Q2 CELL BIOLOGY
Shabnam Fayezi , Sophie Oehms , Helena Wolff von Gudenberg , Maharajah Ponnaiah , Marie Lhomme , Thomas Strowitzki , Ariane Germeyer
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引用次数: 0

摘要

背景:卵巢体细胞支持卵母细胞的成熟和生育。这些细胞中脂肪酸的代谢去饱和对卵母细胞的成熟有积极的旁分泌影响。我们假设颗粒细胞中的硬脂酰-CoA 去饱和酶 1(SCD1)通过维持饱和与不饱和脂质之间的平衡来调节这些细胞分泌的外泌体的脂质货物。我们研究了在与生理相关的体外条件下,SCD1对积液-颗粒细胞模型中外泌体脂质含量的影响:方法:对非黄体化的人 COV434 颗粒细胞单独使用 SCD1 抑制剂(SCDinhib)、与油酸联合使用或在对照条件下进行处理。随后,外泌体被分离出来,并通过纳米颗粒追踪分析、透射电子显微镜和 Western 印迹法进行表征。我们使用液相色谱质谱法研究了脂质体概况。我们使用 TaqMan 引物进行定量 PCR,以评估参与脂肪生成和控制细胞周期进程的基因的表达:结果:在使用SCD1抑制剂处理的细胞中,观察到外泌体产生的趋势,而且外泌体的体积变小。当 SCDinhib 与油酸补充剂结合使用时,这一趋势达到统计学意义。抑制 SCD1 会导致外泌体中饱和欧米加 6 脂类的积累。补充油酸可逆转后一种效应,补充油酸还能改善外泌体的生成,抑制脂肪酸合成酶和细胞周期蛋白 D2 的表达:这些发现强调了新脂肪酸脱饱和在调节特定脂质通过外泌体输出中的关键作用,对控制卵巢内的细胞间通讯具有潜在影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

De novo synthesis of monounsaturated fatty acids modulates exosome-mediated lipid export from human granulosa cells

De novo synthesis of monounsaturated fatty acids modulates exosome-mediated lipid export from human granulosa cells

Background

Ovarian somatic cells support the maturation and fertility of oocytes. Metabolic desaturation of fatty acids in these cells has a positive paracrine impact on the maturation of oocytes. We hypothesized that the enzyme stearoyl-CoA desaturase 1 (SCD1) in granulosa cells regulates the lipid cargo of exosomes secreted from these cells by maintaining the balance between saturated and unsaturated lipids. We investigated the effect of SCD1 on exosome lipid content in a cumulus-granulosa cell model under physiologically relevant in vitro conditions.

Methods

Non-luteinized human COV434 granulosa cells were subjected to treatment with an inhibitor of SCD1 (SCDinhib) alone, in combination with oleic acid, or under control conditions. Subsequently, the exosomes were isolated and characterized via nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. We used liquid chromatography mass spectrometry to investigate the lipidomic profiles. We used quantitative PCR with TaqMan primers to assess the expression of genes involved in lipogenesis and control of cell cycle progression.

Results

A trend toward exosome production was observed with a shift toward smaller exosome sizes in cells treated with SCD1inhib. This trend reached statistical significance when SCDinhib was combined with oleic acid supplementation. SCD1 inhibition led to the accumulation of saturated omega-6 lipids in exosomes. The latter effect was reversed by oleic acid supplementation, which also improved exosome production and suppressed the expression of fatty acid synthase and Cyclin D2.

Conclusion

These findings underscore the critical role of de novo fatty acid desaturation in the regulation of the export of specific lipids through exosomes, with potential implications for controlling intercellular communication within the ovary.

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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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