Biology subjects

Prins, J.

Publications and source records attributed to Prins, J..

3 recordsLinked to original sources

bioRxiv2025

MATERNAL OBESITY MODULATES FOXO1 ACTIVATION AND ADIPOGENESIS IN NEONATAL MESENCHYMAL STEM CELLS

Maternal obesity contributes to increase adiposity in the offspring. The fetal environment is crucial in determining the number of progenitor cells available for adipocyte formation and the extent of fat depots. In this context, adipogenesis is regulated by an intricate network of transcription factors, including FOXO1, which are responsive to external stimuli and ultimately result in the expression of the adipogenic marker PPARG. We hypothesized that the adipocyte progenitor cells, mesenchymal stem cells (MSCs), from neonates of women with obesity would exhibit a differential activation of the SIRT2-FOXO1-PPARG pathway, which is crucial in the regulation of early adipogenesis. In this study we isolated Whartons jelly-derived MSCs from neonates of women with obesity (BMI>30 kg/m{superscript 2}, OB-MSCs) and women with normal-weight (BMI <25 kg/m{superscript 2}, NW-MSCS) and induced them towards in vitro adipogenesis. OB-MSCs showed higher levels of FOXO1 and lower levels of acetyl-FOXO1 compared to NW-MSCs (p<0.05) and differential regulation of these proteins during early adipogenesis of OB-MSCs versus NW-MSCs (p<0.05). Further, acetyl-FOXO1 was higher in the cytoplasm as compared to NW-MSCs upon day 2 of adipogenesis (p<0.05). Finally, we found higher PPARG gene expression in OB-MSCs adipocytes compared with NW-MSCs adipocytes at day 21 of differentiation (p<0.05), denoting higher adipogenic potential. Our findings suggest that the maternal obesogenic environment influences the early modulation of FOXO1, which could lead to an increased adipogenic differentiation in MSCs from neonates of women with obesity, potentially increasing adipogenesis from their precursor pool. This could explain the higher adiposity in neonates of woman with obesity compared to normal-weight woman.

physiology↗

bioRxiv2025

Profiling the secretome: maternal obesity impacts redox and adipogenix signaling molecules during neonatal mesenchymal stem cells' adipogenesis

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. Whartons jelly-derived MSCs were isolated from newborns of normal-weight women (NW-MSC; Body Mass Index 18.5-24.5 kg/m{superscript 2}) and women with obesity (OB-MSC; Body Mass Index>30 kg/m{superscript 2}) 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 offsprings adipocytes.

physiology↗

bioRxiv2025

Disrupted stemness and redox homeostasis in mesenchymal stem cells of neonates from mothers with obesity: implications for increased adiposity

Maternal obesity is a risk factor for increased fetal adiposity. The underlying mechanisms remain unclear, however, emerging evidence suggests that mesenchymal stem cells (MSCs), which are the precursors of adipocytes, from neonates of mothers with obesity exhibit enhanced adipogenic differentiation potential. We hypothesise that the MSCs of neonates from mothers with obesity have different stemness potential and redox state compared to the MSCs from mothers with normal weight. MSCs were isolated from neonates of women with obesity (BMI>30 kg/m{superscript 2}, OB-MSCs) and women with normal weight (BMI <25 kg/m{superscript 2}, NW-MSCs). OB-MSCs showed reduced stemness potential, as seen by a lower OCT3/4 expression and lower clonogenic capacity, than NW-MSCs (p<0.05). In addition, OB-MSCs showed higher levels of mitochondrial superoxide (O2*-), together with lower antioxidant SOD2 gene expression, compared to NW-MSCs (p<0.05). Conversely, OB-MSCs had higher levels of glutathione (GSH) compared to NW-MSCs (p<0.05). Upon exposure to H2O2 (250 M), OB-MSCs displayed attenuated antioxidant response, with lower SOD1, SOD2 and GPX1 gene expression as compared to NW-MSCs (p<0.05). Upon exposure to higher oxidative stress (H2O2, 400 M), total ROS levels were lower in OB-MSCs than in NW-MSCs. In contrast, when challenged for mitochondrial ROS, OB-MSCs showed higher levels of mitochondrial superoxide production as compared to NW-MSCs (p<0.05). Our results indicate that OB-MSCs have lower stemness potential, elevated mitochondrial O2*- and a different basal and oxidative stress-induced redox profile compared to NW-MSCs. These changes in OB-MSCs could predispose them to an increase adipogeneic commitment. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/648714v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1638346org.highwire.dtl.DTLVardef@3f9caaorg.highwire.dtl.DTLVardef@46925eorg.highwire.dtl.DTLVardef@1336dfa_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗