Adipocyte hypertrophy in mesenchymal stem cells from infants of mothers with obesity
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Published on: March 2, 2020
Madeline Rose Keleher1,2, Shreya Shubhangi1, Asya Brown1
1Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Insights
Mesenchymal stem cells (MSCs) from infants of obese mothers show increased fat cell size and altered gene expression, predicting childhood adiposity. These Ob-MSCs exhibit intrinsic tendencies toward larger fat cells and reduced cell division during development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Metabolic Health
Background:
- Infant mesenchymal stem cells (MSCs) adipocyte fat content predicts childhood adiposity.
- Maternal obesity is a risk factor for childhood obesity.
- Understanding early cellular mechanisms is crucial for preventing obesity.
Purpose of the Study:
- To investigate if MSCs from infants of obese mothers (Ob-MSCs) show differences in adipocyte development compared to MSCs from infants of normal-weight mothers (NW-MSCs).
- To identify potential molecular pathways involved in altered adipogenesis in Ob-MSCs.
Main Methods:
- Adipogenesis was induced in MSCs within 3D hydrogels.
- Cell size, number, proliferation, and adipogenesis markers were quantified.
- RNA sequencing analyzed gene expression and pathway enrichment.
Main Results:
- Ob-MSCs had higher zinc finger protein (Zfp)423 levels in undifferentiated cells.
- Adipocytes derived from Ob-MSCs were larger but fewer in number (hypertrophy, reduced hyperplasia).
- Zfp423 correlated with genes in cell cycle, inflammation, and metabolism pathways; Ob-MSC proliferation declined faster post-induction.
Conclusions:
- Ob-MSCs possess an intrinsic predisposition for adipocyte hypertrophy and reduced hyperplasia in vitro.
- Elevated Zfp423 and altered cell cycle gene expression may underlie these Ob-MSC adipogenesis perturbations.
- These findings suggest early cellular differences in MSCs may contribute to later childhood adiposity.
Objective:
Fat content of adipocytes derived from infant umbilical cord mesenchymal stem cells (MSCs) predicts adiposity in children through 4 to 6 years of age. This study tested the hypothesis that MSCs from infants born to mothers with obesity (Ob-MSCs) exhibit adipocyte hypertrophy and perturbations in genes regulating adipogenesis compared with MSCs from infants of mothers with normal weight (NW-MSCs).
Methods:
Adipogenesis was induced in MSCs embedded in three-dimensional hydrogel structures, and cell size and number were measured by three-dimensional imaging. Proliferation and protein markers of proliferation and adipogenesis in undifferentiated and adipocyte differentiating cells were measured. RNA sequencing was performed to determine pathways linked to adipogenesis phenotype.
Results:
In undifferentiated MSCs, greater zinc finger protein (Zfp)423 protein content was observed in Ob- versus NW-MSCs. Adipocytes from Ob-MSCs were larger but fewer than adipocytes from NW-MSCs. RNA sequencing analysis showed that Zfp423 protein correlated with mRNA expression of genes enriched for cell cycle, MSC lineage specification, inflammation, and metabolism pathways. MSC proliferation was not different before differentiation but declined faster in Ob-MSCs upon adipogenic induction.
Conclusions:
Ob-MSCs have an intrinsic propensity for adipocyte hypertrophy and reduced hyperplasia during adipogenesis in vitro, perhaps linked to greater Zfp423 content and changes in cell cycle pathway gene expression.
