Profiling the secretome: maternal obesity impacts redox and adipogenic signaling during neonatal mesenchymal stem cell adipogenesis.

Recent studies evidence an altered bioenergetic profile and higher adipogenic commitment in the mesenchymal stem cells (MSC) from neonates of mothers with obesity. We hypothesize that these alterations may also affect the secretome of these cells. The aim of this study was to characterize the secretome of MSCs from the offspring of women with obesity compared to the ones from normal-weight women, both before and during adipogenesis. Wharton's jelly-derived MSCs were isolated from newborns of normal-weight women (NW-MSC; Body Mass Index 18.5-24.5 kg/m2) and women with obesity (OB-MSC; Body Mass Index > 30 kg/m2) and cultured for 0, 5, and 21 days of adipogenesis. The secretome from these cells was collected during the three timepoints and characterized by mass spectrometry. Our findings reveal fundamental differences in the secretome profiles, primarily associated with pathways involved in cellular and metabolic processes. Maternal obesity was found to decrease redox capacity at day 0 but subsequently triggered a compensatory increase in redox proteins during adipogenesis of OB-MSCs. Additionally, OB-MSCs secreted higher levels of lipid synthesis-related proteins and proinflammatory adipokines, which may contribute to the dysregulated adipogenesis observed in obesity. These preliminary data indicate that maternal obesity programs the secretome of neonatal MSCs, supporting the hypothesis that maternal obesity imprints early progenitor cells and potentially dictates the future metabolic status of the offspring's adipocytes.