Bellalta, S.; Pinheiro-Machado, E.; Prins, J.; Casanello, P.; Faas, M.; Plosch, T.

Recent studies evidence an altered bioenergetic profile and higher adipogenic commitment in the MSCs 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 redox and adipogenic secretome of MSCs from the offspring of women with obesity compared to the ones from normal-weight women, both before and during adipogenesis. Wharton 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 through mass spectrometry. Our findings reveal fundamental difference in the secretome profiles, primarily associated with pathways involved in cellular and metabolic processes (p<0.05). 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 (p<0.05). Additionally, OB-MSCs secreted higher levels of lipid synthesis proteins and proinflammatory adipokines (p<0.05), which may contribute to the dysregulated adipogenesis observed in obesity. These results indicate that maternal obesity programs the secretome of neonatal MSCs, supporting that maternal obesity imprints early progenitor cells, potentially dictating the future metabolic status of the offspring adipocytes.