Infant Mesenchymal Stem Cell Insulin Action Is Associated with Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study

Abstract: Preclinical rodent and non-human primate models investigating maternal obesity have highlighted the importance of the intrauterine environment for development of insulin resistance in the offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight (NW) or mothers with obesity (Ob). Insulin stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro. And there was no difference in insulin action based on maternal obesity. However, maternal free fatty acid concentration, cord leptin, and intracellular triglyceride content were positively correlated with insulin action. Furthermore, MSCs from offspring born to mothers with elevated FFA displayed elevated activation of the mTOR signaling pathway. Taken together, these data suggest that infants born to mothers with elevated lipid availability have greater insulin action in MSC, which may indicate upregulation of growth and lipid storage pathways during periods of maternal overnutrition.