Adenosine improves postmenopausal obesity by regulating neutrophil extracellular traps.

Abstract

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.