Department of Renal Transplantation, First Affiliated Hospital of Xi'an Jiaotong University, 710061, China; Institute of Organ Transplantation, Xi'an Jiaotong University, 710061, China.
Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Institute of Organ Transplantation, Xi'an Jiaotong University, 710061, China.
Phytomedicine. 2023 Aug;117:154908. doi: 10.1016/j.phymed.2023.154908. Epub 2023 Jun 2.
Abnormal endocrine metabolism caused by polycystic ovary syndrome combined with insulin resistance (PCOS-IR) poses a serious risk to reproductive health in females. Quercitrin is a flavonoid that can efficiently improve both endocrine and metabolic abnormalities. However, it remains unclear if this agent can exert therapeutic effect on PCOS-IR.
The present study used a combination of metabolomic and bioinformatic methods to screen key molecules and pathways involved in PCOS-IR. A rat model of PCOS-IR and an adipocyte IR model were generated to investigate the role of quercitrin in regulating reproductive endocrine and lipid metabolism processes in PCOS-IR.
Peptidase M20 domain containing 1 (PM20D1) was screened using bioinformatics to evaluate its participation in PCOS-IR. PCOS-IR regulation via the PI3K/Akt signaling pathway was also investigated. Experimental analysis showed that PM20D1 levels were reduced in insulin-resistant 3T3-L1 cells and a letrozole PCOS-IR rat model. Reproductive function was inhibited, and endocrine metabolism was abnormal. The loss of adipocyte PM20D1 aggravated IR. In addition, PM20D1 and PI3K interacted with each other in the PCOS-IR model. Furthermore, the PI3K/Akt signaling pathway was shown to participate in lipid metabolism disorders and PCOS-IR regulation. Quercitrin reversed these reproductive and metabolic disorders.
PM20D1 and PI3K/Akt were required for lipolysis and endocrine regulation in PCOS-IR to restore ovarian function and maintain normal endocrine metabolism. By upregulating the expression of PM20D1, quercitrin activated the PI3K/Akt signaling pathway, improved adipocyte catabolism, corrected reproductive and metabolic abnormalities, and had a therapeutic effect on PCOS-IR.
多囊卵巢综合征合并胰岛素抵抗（PCOS-IR）引起的异常内分泌代谢对女性生殖健康构成严重威胁。槲皮素是一种类黄酮，能有效改善内分泌和代谢异常。然而，槲皮素是否对 PCOS-IR 具有治疗作用尚不清楚。
本研究采用代谢组学和生物信息学相结合的方法筛选 PCOS-IR 相关的关键分子和通路。建立 PCOS-IR 大鼠模型和脂肪细胞胰岛素抵抗模型，研究槲皮素调节 PCOS-IR 生殖内分泌和脂质代谢的作用。
利用生物信息学筛选出肽酶 M20 结构域包含蛋白 1（PM20D1），评估其在 PCOS-IR 中的作用。研究了 PM20D1 对 PI3K/Akt 信号通路的调节作用。实验分析表明，胰岛素抵抗的 3T3-L1 细胞和来曲唑 PCOS-IR 大鼠模型中 PM20D1 水平降低。生殖功能受到抑制，内分泌代谢异常。脂肪细胞 PM20D1 的缺失加重了胰岛素抵抗。此外，PM20D1 和 PI3K 在 PCOS-IR 模型中相互作用。此外，PI3K/Akt 信号通路参与脂质代谢紊乱和 PCOS-IR 调节。槲皮素逆转了这些生殖和代谢紊乱。
PM20D1 和 PI3K/Akt 参与了 PCOS-IR 中的脂肪分解和内分泌调节，以恢复卵巢功能并维持正常的内分泌代谢。通过上调 PM20D1 的表达，槲皮素激活了 PI3K/Akt 信号通路，改善了脂肪细胞的分解代谢，纠正了生殖和代谢异常，对 PCOS-IR 具有治疗作用。
