ResearchIn-Press PreviewDevelopmentMetabolism Open Access | 10.1172/jci.insight.180016
1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
Find articles by Gyllenhammer, L. in: JCI | PubMed | Google Scholar
1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
Find articles by Zaegel, V. in: JCI | PubMed | Google Scholar
1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
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1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
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1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
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1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
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1Department of Pediatrics, University of California, Irvine, Irvine, United States of America
2Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States of America
3Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, United States of America
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Published September 3, 2024 - More info
Our objective was to interrogate infant mesenchymal stem cell (MSC) lipid metabolism and gestational exposures 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 (24h 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, tumor necrosis factor-α, high density lipoprotein- and total- cholesterol in fasting blood from mid- and late-gestation (~17, ~27wks). We measured child adiposity at birth (n=29), 4-6m (n=29), and 4-6y (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, though Cluster-2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC Clusters and child adiposity at 4-6y (both highest in Cluster-3). Our data supports 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, though validation with larger longitudinal samples is warranted.