| خلاصه مقاله | Introduction: Adipose tissue functions as a secretory organ, influencing processes beyond energy storage. White and brown adipocytes, which play opposing roles in energy metabolism, exhibit unique paracrine and endocrine roles. Extracellular vesicles (EVs) from these adipocytes show therapeutic potential, yet their cell-specific effects remain poorly understood. This study aimed to assess the impact of EVs from white and brown adipocyte-like cells (WALCs and BALCs) on various human cell types.Methods: This study received local ethics committee approval, and all cell samples were collected under informed consent. Human adipose-derived stem cells (hADSCs) were differentiated into WALCs and BALCs using induction media. Differentiation was verified by lipid droplet accumulation and quantification of adipocyte markers. EVs were isolated from conditioned media (CM) using differential ultracentrifugation and characterized by light scattering, electron microscopy, and marker immunoblotting. Four human cell types—representing stem, somatic, and cancer cells—were treated with purified EVs or crude CM. Cellular responses were evaluated using flow cytometry, qPCR, electrochemiluminescence, and lipidomic profiling via liquid chromatography-tandem mass spectrometry. Results: In hADSCs, all EVs and CM promoted osteogenic differentiation and reduced stemness markers Oct4 and Sox2, with BALC-derived EVs showing the greatest potential to enhance differentiation and WALC-derived EVs most effectively suppressing stemness. When treated with BALC-derived EVs, hADSCs displayed the highest number of differentially expressed lipids, primarily upregulated hits, while umbilical cord stem cells exhibited minimal responses to the treatment. In MCF-7 cancer cells, CM from both adipocyte types had a greater pro-apoptotic effect than EVs. Additionally, BALC-derived EVs induced higher estradiol secretion in ovarian granulosa cells compared to WALCderived EVs. Pathway analysis indicated that BALC-derived EVs promoted lipid storage and membrane remodelling in hADSCs, decreased lipid storage reliance in umbilical stem cells, reduced fatty acid oxidation in MCF-7 cells, and enhanced energy metabolism in granulosa cells. Summary/Conclusion: EVs from WALCs and BALCs cells exert distinct, cell-specific effects compared to soluble factors, underscoring their role in mediating cell-cell communication. These findings provide insights into the potential applications of adipocyte-derived EVs in non–cell-based therapies. Funding: This study was supported by the Tabriz University of Medical Sciences, Tabriz, Iran (Grant No. 66664) and the University Medical Center Schleswig-Holstein, Leubeck, Germany. The presentation was supported by the COST Action CA21113 SENESCENCE2030, awarded to the last author. |