(P10-080-24) Maternal Obesity Alters Adipogenic Potential and Mitochondrial Function in Mesenchymal Stem Cells From Infants Born to Mothers With Overweight or Obesity

Objectives: The heightened susceptibility of offspring to obesity is notably linked with maternal obesity, with potential implications for programming modifications during adipocyte differentiation. This study sought to examine the adipogenic differentiation response in umbilical cord mesenchymal stem cells (MSC) from mothers with obesity and assess the associations between markers of adipocyte differentiation and maternal/child anthropometric outcomes.

Methods: MSC were cultured the from umbilical cord matrix of infants born to mothers with normal weight (22.2 ± 0.3 kg/m²; n = 31; NW-MSC) or with overweight/obesity (29.3 ± 0.6 kg/m²; n = 33; OW/OB-MSC). Cultured MSC were collected prior to adipocyte differentiation (day 0) and at day 7 and day 14 into differentiation. Gene expression of markers of adipocyte differentiation (PPARGand CEBPA) was analyzed by qRT-PCR. A Seahorse XF Mito stress test was performed to evaluate differences in oxygen consumption rate. Children’s body composition was analyzed at intervals up to 24 months of age using quantitative nuclear magnetic resonance. Pearson correlations were used to evaluate relationships between markers of adipocyte differentiation and maternal BMI or children fat mass index (FMI, kg fat mass/m²).

Results: Expression of PPARG during differentiation was not associated with BMI in both maternal groups (P ≥ 0.47). However, in OW/OB-MSC at day 14 of differentiation, CEBPA expression was negatively associated with maternal BMI (r = -0.38, P < 0.02). Expression of PPARG in OW/OB-MSC on day 14 of differentiation tended to positively correlate with child fat mass index at 2 weeks of age (r = 0.3, P = 0.07) and at 6 months of age (r = 0.4, P = 0.01) whereas no relationships were observed for NW-MSC. Expression of CEBPA at day 14 of differentiation tended to positively correlate with child fat mass index at 24 months of age including data from both maternal groups (r = 0.25, P = 0.08). Both maximal respiration and spare respiratory capacity tended (P = 0.07) to be lower in OW/OB-MSC at day 7 of differentiation compared to NW-MSC.

Conclusions: The observed correlation among gene expression, maternal BMI, and children's FMI implies a potential influence of maternal BMI on the adipogenic differentiation of mesenchymal stem cells.

Funding Sources: USDA-ARS Project 6026-51000-012-06 S