Wang Anzhu, Zhang Wei, Kang Mengjiao, Wang Shan, Shi Jingjing, Xie Pengfei, Zhao Linhua, Tong Xiaolin
National Center for Integrative Medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730101, Gansu, China.
Sci Rep. 2025 Jul 9;15(1):24653. doi: 10.1038/s41598-025-06379-x.
Postmenopause marks a critical physiological transition in women, triggering changes in fat distribution and promoting obesity, which is strongly linked to systemic low-grade chronic inflammation, with neutrophil extracellular traps (NETs) playing a pivotal role in this process. Differentially expressed genes (DEGs) related to obesity were identified from the GEO database (GSE44000), followed by protein-protein interaction (PPI) network construction and functional enrichment analysis. Immune infiltration analysis was performed to assess changes in the adipose tissue microenvironment. In vivo, a bilateral ovariectomized (OVX) mouse model was employed to evaluate the effects of adenosine on obesity. RT-qPCR and Western blot were used to assess gene expression and NETs markers. A total of 510 DEGs were identified, with 469 upregulated genes primarily linked to inflammation and immune infiltration. PPI analysis highlighted key genes involved in NETs formation. Immune infiltration analysis revealed significant immune microenvironment alterations. Adenosine treatment in OVX mice reduced body weight, fat tissue, liver lipid deposition, and NETs markers (ELANE, MPO), downregulating TNF, ITGB2, and ITGAM. Adenosine ameliorates postmenopausal obesity by regulating markers of NETs, underscoring the critical role of inflammation in obesity pathogenesis and offering a potential novel therapeutic approach.
绝经后期标志着女性关键的生理转变，引发脂肪分布变化并促进肥胖，而肥胖与全身性低度慢性炎症密切相关，中性粒细胞胞外诱捕网（NETs）在此过程中起关键作用。从基因表达综合数据库（GEO数据库，GSE44000）中鉴定出与肥胖相关的差异表达基因（DEGs），随后构建蛋白质-蛋白质相互作用（PPI）网络并进行功能富集分析。进行免疫浸润分析以评估脂肪组织微环境的变化。在体内，采用双侧卵巢切除（OVX）小鼠模型评估腺苷对肥胖的影响。使用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法评估基因表达和NETs标志物。共鉴定出510个DEGs，其中469个上调基因主要与炎症和免疫浸润相关。PPI分析突出了参与NETs形成的关键基因。免疫浸润分析揭示了免疫微环境的显著改变。对OVX小鼠进行腺苷治疗可降低体重、脂肪组织、肝脏脂质沉积以及NETs标志物（弹性蛋白酶（ELANE）、髓过氧化物酶（MPO）），下调肿瘤坏死因子（TNF）、整合素β2（ITGB2）和整合素αM（ITGAM）。腺苷通过调节NETs标志物改善绝经后肥胖，强调了炎症在肥胖发病机制中的关键作用，并提供了一种潜在的新型治疗方法。
