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JCI Insight. 2017 Nov 2;2(21). pii: 94200. doi: 10.1172/jci.insight.94200.

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism.

Author information

1
Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
2
Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
3
Colorado Biostatistics Consortium, Aurora, Colorado, USA.

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.

PMID:
29093265
PMCID:
PMC5752288
DOI:
10.1172/jci.insight.94200
[Indexed for MEDLINE]
Free PMC Article

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