Investigating the Impact of Maternal Exercise on Substrate Oxidation in Fetal Mesenchymal Stem Cells from Mothers with Overweight and Obesity

Abstract

Background: Maternal obesity is associated with adverse metabolic programming in offspring, including increased risk of obesity, insulin resistance, and metabolic syndrome. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that the intrauterine environment during fetal development critically influences long-term health outcomes. Maternal obesity creates an adverse intrauterine environment by chronic low-grade inflammation and unfavorable epigenetic reprogramming. However, maternal exercise during pregnancy attenuates these adverse effects and improves offspring metabolic health. Mesenchymal stem cells (MSCs), which serve as progenitors for multiple tissue types including adipose tissue, muscle, and bone, may represent a key mechanism through which maternal exercise influences offspring metabolic outcomes. Purpose: This study investigates whether maternal exercise during pregnancy improves offspring metabolic programming, specifically glucose oxidation and fatty acid oxidation in fetal mesenchymal stem cells, in women with overweight and obesity. We hypothesized that maternal exercise enhances glucose and fatty acid oxidation in fetal MSCs from mothers with overweight and obesity, leading to improved metabolic health and reduced infant adiposity. Methods: 52 pregnant women aged 18-35 years with pre-pregnancy BMI 25.1-44.6 kg/m2 were randomized into four exercise groups. Fetal mesenchymal stem cells were isolated from umbilical cord at birth and assessed for substrate metabolism using radiolabeled tracer techniques. Glucose oxidation was measured under basal and insulin-stimulated conditions with [14C]-labeled substrates. Fatty acid oxidation and glycogen synthesis were measured using [14C]-labeled substrates. Results: Maternal exercise significantly enhanced glucose oxidation under basal conditions (p = 0.03) and insulin-stimulated conditions (p = 0.01). Resistance exercise produced the most pronounced improvements among four exercise modalities (basal; p = 0.02, insulin; p = 0.01). The improvement in glucose oxidation was independent of insulin stimulation. Maternal exercise also enhanced fatty acid partitioning toward complete oxidation for oleate (p = 0.01) and palmitate (p = 0.01), demonstrating improved metabolic flexibility. Resistance exercise and Aerobic exercise demonstrated greater effects on complete fatty acid oxidation compared to the combined exercise. Glycogen synthesis was unchanged across all groups. Conclusion: Maternal exercise during pregnancy significantly improves fetal mesenchymal stem cell glucose and fatty acid oxidation in offspring of women with overweight and obesity. Resistance exercise emerged as the most effective modality for fetal metabolic programming. These findings demonstrate that maternal exercise is a potent intervention for counteracting obesity-induced fetal metabolic dysfunction and may interrupt the intergenerational transmission of metabolic disease.