棕色脂肪组织衍生的外泌体通过 STAT3/GPX4 信号通路改善小鼠的多囊卵巢综合征

IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yu-Qing Fang, Han-Ke Zhang, Qiong-Qiong Wei, Yan-Hui Li
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引用次数: 0

摘要

多囊卵巢综合征(PCOS)与脂肪组织生理功能受损有关。棕色脂肪组织(BAT)质量或活性的升高已显示出治疗多囊卵巢综合征的潜力。在这项研究中,我们的目的是调查棕色脂肪组织衍生的外泌体(BAT-Exos)作为棕色脂肪组织活性的潜在生物标志物,在治疗多囊卵巢综合征方面是否具有与棕色脂肪组织相似的功效。给雌性C57BL/6J小鼠口服1毫克/千克来曲唑21天,诱发多囊卵巢综合征。随后,动物接受 BAT 移植或通过尾静脉注射从年轻健康小鼠体内分离出的 BAT-Exos(200 μg);健康雌性小鼠作为对照组。结果表明,BAT-Exos 治疗可显著降低多囊卵巢综合症小鼠的体重,并改善其胰岛素抵抗。此外,BAT-Exos 还能通过逆转发情周期的非周期性、降低循环中的黄体生成素和睾酮、恢复卵巢性能和改善卵母细胞质量来改善排卵功能,从而提高妊娠率和产仔数。此外,Western 印迹显示 BAT-Exos 组小鼠卵巢中信号转导和激活转录 3(STAT3)的表达减少,而谷胱甘肽过氧化物酶 4(GPX4)的表达增加。为了进一步探索 STAT3/GPX4 信号通路在多囊卵巢综合征小鼠中的作用,我们向小鼠腹腔注射了 5 mg/kg STAT3 抑制剂 stattic。与 BAT-Exos 治疗一致的是,施用 stattic 能挽救来曲唑诱导的多囊卵巢综合征表型。这些研究结果表明,BAT-Exos治疗可能是治疗多囊卵巢综合征的一种潜在策略,STAT3/GPX4信号通路是多囊卵巢综合征的一个关键治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway

Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway

Polycystic ovary syndrome (PCOS) is associated with impaired adipose tissue physiology. Elevated brown adipose tissue (BAT) mass or activity has shown potential in the treatment of PCOS. In this study, we aimed to investigate whether BAT-derived exosomes (BAT-Exos), as potential biomarkers of BAT activity, exert similar benefits as BAT in the treatment of PCOS. PCOS was induced in female C57BL/6J mice orally administered 1 mg/kg of letrozole for 21 days. Subsequently, the animals underwent transplantation with BAT or administered BAT-Exos (200 μg) isolated from young healthy mice via the tail vein; healthy female mice were used as controls. The results indicate that BAT-Exos treatment significantly reduced body weight and improved insulin resistance in PCOS mice. In addition, BAT-Exos improved ovulation function by reversing the acyclicity of the estrous cycle, decreasing circulating luteinizing hormone and testosterone, recovering ovarian performance, and improving oocyte quality, leading to a higher pregnancy rate and litter size. Furthermore, western blotting revealed reduced expression of signal transducer and activator of transcription 3 (STAT3) and increased expression of glutathione peroxidase 4 (GPX4) in the ovaries of mice in the BAT-Exos group. To further explore the role of the STAT3/GPX4 signaling pathway in PCOS mice, we treated the mice with an intraperitoneal injection of 5 mg/kg stattic, a STAT3 inhibitor. Consistent with BAT-Exos treatment, the administration of stattic rescued letrozole-induced PCOS phenotypes. These findings suggest that BAT-Exos treatment might be a potential therapeutic strategy for PCOS and that the STAT3/GPX4 signaling pathway is a critical therapeutic target for PCOS.

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来源期刊
FASEB Journal
FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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