Background

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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槲皮苷通过上调 PI3K/Akt 通路中 PM20D1 缓解多囊卵巢综合征-胰岛素抵抗脂质代谢紊乱

背景

多囊卵巢综合征合并胰岛素抵抗（PCOS-IR）引起的内分泌代谢异常对女性生殖健康构成严重风险。槲皮素是一种黄酮类化合物，可以有效改善内分泌和代谢异常。然而，该药物是否能对 PCOS-IR 发挥治疗作用尚不清楚。

方法

本研究结合代谢组学和生物信息学方法来筛选与 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 IR 模型，以研究槲皮苷在调节 PCOS-IR 生殖内分泌和脂质代谢过程中的作用。

结果

使用生物信息学筛选包含 1 (PM20D1) 的肽酶 M20 结构域，以评估其参与 PCOS-IR 的情况。还研究了 PCOS-IR 通过 PI3K/Akt 信号通路的调节。实验分析表明，胰岛素抵抗 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的损失加剧了IR。此外，PM20D1和PI3K在PCOS-IR模型中相互作用。此外，PI3K/Akt 信号通路被证明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。

结论

PCOS-IR的脂肪分解和内分泌调节需要PM20D1和PI3K/Akt来恢复卵巢功能并维持正常的内分泌代谢。槲皮苷通过上调PM20D1的表达，激活PI3K/Akt信号通路，改善脂肪细胞分解代谢，纠正生殖代谢异常，对PCOS-IR具有治疗作用。