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Infant mesenchymal stem cell insulin action is associated with maternal plasma free fatty acids, independent of obesity status: The Healthy Start Study

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posted on 27.05.2022, 14:27 authored by Alec B Chaves, Donghai Zheng, Jonathan A Johnson, Bryan C Bergman, Zachary W Patinkin, Vincent Zaegel, Ericka M Biagioni, Polina Krassovskaia, Nicholas T Broskey, Linda E May, Dana Dabelea, Joseph A Houmard, Kristen E Boyle


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.


This study is supported by the National Institutes of Health (NIH) R01DK117168 to KEB, the American Diabetes Association (1-18-ITCS-016 to KEB), the Environmental Influences on Child Health Outcomes (ECHO) Program (NIH 1UG3OD023248 to DD), American Heart Association (15GRNT24470029 to LEM), and the Foundation Doctoral Student Research Grant (ACSM 19-01128 to ABC). The Healthy Start BabyBUMP Project is supported by grants from the American Heart Association (predoctoral fellowship 14PRE18230008) and by the parent Healthy Start Study (R01 DK076648 to DD), and the Colorado Clinical and Translational Sciences Institute (UL1 TR001082) for maternal visits and collection of birth measures. The Molecular and Cellular Analytical Core of the CU Nutrition Obesity Research Center (NORC) at the University of Colorado Anschutz Medical Campus is supported by NIH DK048520. This project is solely the responsibility of the authors, and this work does not necessarily represent the official views of the NIH.