Obstetrics and Gynecology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Nov 29;12:747944. doi: 10.3389/fendo.2021.747944. eCollection 2021.
Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine, and metabolic disorder in reproductive-age women. In order to explore the active metabolites of brown adipose tissue (BAT) transplantation in improving the reproductive and metabolic phenotypes in a PCOS rat model, the metabolites in the recipient's BAT were explored using the liquid chromatography-mass spectrometry technique. In total, 9 upregulated and 13 downregulated metabolites were identified. They were roughly categorized into 12 distinct classes, mainly including glycerophosphoinositols, glycerophosphocholines, and sphingolipids. Ingenuity pathway analysis predicted that these differentially metabolites mainly target the PI3K/AKT, MAPK, and Wnt signaling pathways, which are closely associated with PCOS. Furthermore, one of these differential metabolites, sphingosine belonging to sphingolipids, was randomly selected for further experiments on a human granulosa-like tumor cell line (KGN). It significantly accelerated the apoptosis of KGN cells induced by dihydrotestosterone. Based on these findings, we speculated that metabolome changes are an important process for BAT transplantation in improving PCOS. It might be a novel therapeutic target for PCOS treatment.
多囊卵巢综合征(PCOS)是一种发生于育龄期妇女的复杂生殖、内分泌和代谢紊乱性疾病。为了探讨棕色脂肪组织(BAT)移植对多囊卵巢综合征大鼠模型生殖和代谢表型的改善作用中的活性代谢物,本研究采用液相色谱-质谱联用技术对接受者的 BAT 中的代谢物进行了探索。共鉴定出 9 个上调和 13 个下调的代谢物。它们大致分为 12 个不同的类别,主要包括甘油磷酸肌醇、甘油磷酸胆碱和鞘脂类。通路分析预测,这些差异代谢物主要针对 PI3K/AKT、MAPK 和 Wnt 信号通路,这些通路与 PCOS 密切相关。此外,鞘脂类中的鞘氨醇被随机选择用于进一步研究人颗粒状细胞瘤系(KGN)。它显著加速了双氢睾酮诱导的 KGN 细胞凋亡。基于这些发现,我们推测代谢组学变化是 BAT 移植改善 PCOS 的一个重要过程。它可能是 PCOS 治疗的一个新的治疗靶点。