Lipidomics of infant mesenchymal stem cells associate with the maternal milieu and child adiposity

Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis...

Full description

Saved in:
Bibliographic Details
Published in:JCI insight 2024-09, Vol.9 (19)
Main Authors: Gyllenhammer, Lauren E, Zaegel, Vincent, Duensing, Allison M, Lixandrao, Manoel E, Dabelea, Dana, Bergman, Bryan C, Boyle, Kristen E
Format: Article
Language:English
Subjects:
Adiposity
Adult
AMP-Activated Protein Kinases - metabolism
Child
Child, Preschool
Fatty Acids - metabolism
Female
Humans
Infant
Infant, Newborn
Lipid Metabolism
Lipidomics - methods
Male
Mesenchymal Stem Cells - metabolism
Obesity - metabolism
Pediatric Obesity - metabolism
Pregnancy
Triglycerides - metabolism
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis in vitro, we used lipidomics to distinguish phenotypes by unbiased cluster analysis and lipid challenge (24-hour excess fatty acid [24hFA]). We measured MSC AMP-activated protein kinase (AMPK) activity and fatty acid oxidation (FAO), and a composite index of maternal glucose, insulin, triglycerides, free fatty acids, TNF-α, and high-density lipoprotein and total cholesterol in fasting blood from mid and late gestation (~17 and ~27 weeks, respectively). We measured child adiposity at birth (n = 29), 4-6 months (n = 29), and 4-6 years (n = 13). Three MSC clusters were distinguished by triacylglycerol (TAG) stores, with greatest TAGs in Cluster 2. All clusters increased acylcarnitines and TAGs with 24hFA, although Cluster 2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC clusters and child adiposity at 4-6 years (both highest in Cluster 3). Our data support the notion that MSC phenotypes are predicted by comprehensive maternal metabolic milieu exposures, independent of maternal BMI, and suggest utility as an at-birth predictor for child adiposity, although validation with larger longitudinal samples is warranted.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.180016