Brown and white adipocyte like cells derived exosomes differentially regulate stemness, hormone secretion, apoptosis, and lipid metabolism in model cells

Abstract

White and brown adipocytes show therapeutic potential, yet their exosomes mediated cell-specific effects remain poorly understood. This study aimed to assess the impact of conditioned media (CM) or exosomes derived from brown and white adipocyte-like cells (BALCs and WALCs, respectively) on four human cell types, including ovarian granulosa cells (OGCs), MCF-7 breast cancer cells, human adipose-derived stem cells (hADSCs), and human umbilical cord mesenchymal stem cells (hUCMSCs). Isolated hADSCs were differentiated into BALCs and WALCs using specific induction media. Corresponding exosomes were isolated from BALCs or WALCs derived CM and characterized. Human cell types—representing stem, somatic, and cancer cells—were treated with CM or exosomes. Cellular responses and lipidomic profiling were evaluated using molecular biology techniques and mass spectrometry, respectively. BALCs-derived exosomes significantly increased estradiol secretion from ovarian granulosa cells (p < 0.05). In MCF-7 cells, CM had a stronger pro-apoptotic effect than exosomes (>2-fold). In hADSCs, both CM and exosomes promoted osteogenic differentiation (2.3-fold) and reduced stemness markers proteins Oct4 and Sox2 (p < 0.05). When treated with BALCs-derived exosomes, hADSCs displayed the highest number of differentially expressed lipids, primarily upregulated hits. Pathway analysis indicated that BALCs-derived exosomes promoted lipid storage and membrane remodeling in hADSCs, enhanced energy metabolism in granulosa cells, reduced fatty acid oxidation in MCF-7 cells, and decreased lipid storage in hUCMSCs. Our results highlight a potential modulatory role of adipocyte-derived exosomes in intercellular communication. The findings of this study may be applicable in regenerative medicine, metabolic regulation and cancer therapeutic approaches.