Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism
Peter R Baker1, Zachary Patinkin1, Allison Lb Shapiro2
1Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
Insights
Maternal obesity impacts infant metabolism, altering cell development and increasing obesity risk. Stem cells from infants of obese mothers show distinct metabolic and gene expression changes, revealing early developmental programming.
Area of Science:
- Developmental Biology
- Metabolic Health
- Obesity Research
Background:
- Maternal obesity is a significant global health concern, elevating offspring's risk for obesity.
- Understanding early developmental programming in infants at risk for obesity is crucial but hindered by sampling limitations.
- Umbilical cord-derived mesenchymal stem cells (uMSC) offer a viable model for studying in-utero exposures and developmental trajectories.
Purpose of the Study:
- To investigate differences in energy metabolism and gene expression in uMSC from infants of normal-weight versus obese mothers.
- To determine the correlation between maternal obesity, maternal lipid levels, and neonatal adiposity with cellular metabolism in uMSC.
- To elucidate potential developmental programming mechanisms contributing to obesity risk in offspring of obese mothers.
Main Methods:
- Collected uMSC from newborns of normal-weight and obese mothers.
- Differentiated uMSC into myocytes and adipocytes to analyze metabolic and gene expression profiles.
- Correlated cellular findings with maternal obesity status, maternal lipid levels, and neonatal adiposity.
Main Results:
- uMSC myocytes from offspring of obese mothers exhibited biomarkers of incomplete beta-oxidation linked to infant adiposity and maternal lipids.
- Differential gene expression analysis revealed enrichment of metabolic and biosynthetic processes associated with maternal obesity.
- uMSC adipocytes showed maternal obesity and lipid-associated downregulation of insulin-dependent energy-sensing pathways (PI3K, AMPK) and altered mitochondrial activity.
Conclusions:
- Cell-specific alterations in metabolism and gene expression in newborn uMSC correlate with maternal obesity and offspring adiposity.
- These findings suggest tissue-specific metabolic and regulatory changes occurring during early development.
- The study provides critical insights into the developmental programming of obesity risk in offspring exposed to maternal obesity.
Abstract:
Maternal obesity is a global health problem that increases offspring obesity risk. The metabolic pathways underlying early developmental programming in human infants at risk for obesity remain poorly understood, largely due to barriers in fetal/infant tissue sampling. Utilizing umbilical cord-derived mesenchymal stem cells (uMSC) from offspring of normal weight and obese mothers, we tested whether energy metabolism and gene expression differ in differentiating uMSC myocytes and adipocytes, in relation to maternal obesity exposures and/or neonatal adiposity. Biomarkers of incomplete β-oxidation were uniquely positively correlated with infant adiposity and maternal lipid levels in uMSC myocytes from offspring of obese mothers only. Metabolic and biosynthetic processes were enriched in differential gene expression analysis related to maternal obesity. In uMSC adipocytes, maternal obesity and lipids were associated with downregulation in multiple insulin-dependent energy-sensing pathways including PI3K and AMPK. Maternal lipids correlated with uMSC adipocyte upregulation of the mitochondrial respiratory chain but downregulation of mitochondrial biogenesis. Overall, our data revealed cell-specific alterations in metabolism and gene expression that correlated with maternal obesity and adiposity of their offspring, suggesting tissue-specific metabolic and regulatory changes in these newborn cells. We provide important insight into potential developmental programming mechanisms of increased obesity risk in offspring of obese mothers.
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