Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis
<b>Background:</b> Polycystic ovary syndrome (PCOS) is a leading cause of infertility but also a metabolic disorder, frequently associated with obesity, insulin resistance, and diabetes. However, its etiology remains inadequately understood. Recent studies have increasingly implicated ne...
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2025-04-01
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| author | Siyu Lin Yushan Li Wei Liu Yanzhi Du Tao Tao |
| author_facet | Siyu Lin Yushan Li Wei Liu Yanzhi Du Tao Tao |
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| description | <b>Background:</b> Polycystic ovary syndrome (PCOS) is a leading cause of infertility but also a metabolic disorder, frequently associated with obesity, insulin resistance, and diabetes. However, its etiology remains inadequately understood. Recent studies have increasingly implicated neutrophil extracellular traps (NETs) in the pathogenesis of metabolic diseases. <b>Methods:</b> Serum and follicular fluid samples were collected from patients with PCOS and control populations to assess NETs levels. The effects of NETs were investigated using DNase I to reduce NETs in dehydroepiandrosterone sulfate (DHEAS)-induced PCOS rats. Metabolic differences were further analyzed by untargeted metabolomics, and in vitro studies were conducted using primary bone marrow-derived neutrophils and normal mouse liver cell lines. <b>Results:</b> Markers of NETs in both the serum and follicular fluid of patients with PCOS were significantly higher than those in the control group. PCOS rats treated with DNase I exhibited significant improvements in glucose metabolism. Untargeted metabolomics analysis of liver tissue from these rats revealed alterations in the glycolysis pathway. Subsequent in vitro experiments demonstrated that treatment with NETs-conditioned medium (NETs CM) led to reduced insulin sensitivity, glucose uptake, and glucose utilization in liver cells, accompanied by varying degrees of decline in the transcription, translation, and function of glycolysis pathway proteins. <b>Conclusions:</b> NETs may be involved in the regulation of insulin resistance pathogenesis in PCOS by downregulating glycolytic pathways in the liver. Our study offers a novel strategy for insulin resistance intervention in PCOS. |
| format | Article |
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| spelling | doaj-art-3e7de5a9ff2740b3955af4cb401afff72025-08-20T03:14:17ZengMDPI AGBiomolecules2218-273X2025-04-0115457210.3390/biom15040572Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic GlycolysisSiyu Lin0Yushan Li1Wei Liu2Yanzhi Du3Tao Tao4Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaCenter for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, ChinaDepartment of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China<b>Background:</b> Polycystic ovary syndrome (PCOS) is a leading cause of infertility but also a metabolic disorder, frequently associated with obesity, insulin resistance, and diabetes. However, its etiology remains inadequately understood. Recent studies have increasingly implicated neutrophil extracellular traps (NETs) in the pathogenesis of metabolic diseases. <b>Methods:</b> Serum and follicular fluid samples were collected from patients with PCOS and control populations to assess NETs levels. The effects of NETs were investigated using DNase I to reduce NETs in dehydroepiandrosterone sulfate (DHEAS)-induced PCOS rats. Metabolic differences were further analyzed by untargeted metabolomics, and in vitro studies were conducted using primary bone marrow-derived neutrophils and normal mouse liver cell lines. <b>Results:</b> Markers of NETs in both the serum and follicular fluid of patients with PCOS were significantly higher than those in the control group. PCOS rats treated with DNase I exhibited significant improvements in glucose metabolism. Untargeted metabolomics analysis of liver tissue from these rats revealed alterations in the glycolysis pathway. Subsequent in vitro experiments demonstrated that treatment with NETs-conditioned medium (NETs CM) led to reduced insulin sensitivity, glucose uptake, and glucose utilization in liver cells, accompanied by varying degrees of decline in the transcription, translation, and function of glycolysis pathway proteins. <b>Conclusions:</b> NETs may be involved in the regulation of insulin resistance pathogenesis in PCOS by downregulating glycolytic pathways in the liver. Our study offers a novel strategy for insulin resistance intervention in PCOS.https://www.mdpi.com/2218-273X/15/4/572polycystic ovary syndrome (PCOS)neutrophil extracellular traps (NETs)insulin resistanceuntargeted metabolomics |
| spellingShingle | Siyu Lin Yushan Li Wei Liu Yanzhi Du Tao Tao Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis Biomolecules polycystic ovary syndrome (PCOS) neutrophil extracellular traps (NETs) insulin resistance untargeted metabolomics |
| title | Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis |
| title_full | Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis |
| title_fullStr | Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis |
| title_full_unstemmed | Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis |
| title_short | Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis |
| title_sort | metabolic implications of elevated neutrophil extracellular traps in polycystic ovary syndrome a focus on hepatic glycolysis |
| topic | polycystic ovary syndrome (PCOS) neutrophil extracellular traps (NETs) insulin resistance untargeted metabolomics |
| url | https://www.mdpi.com/2218-273X/15/4/572 |
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