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Cited by 115Mesenchymal stem cell researchAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Mesenchymal Stem Cells From Infants Born to Obese Mothers Exhibit Greater Potential for Adipogenesis: The Healthy Start BabyBUMP Project

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Boyle, Kristen E., Patinkin, Zachary W., Shapiro, Allison L.B., Baker, Peter R., Dabelea, Dana, Friedman, Jacob E.·2016·Diabetes
DOI 10.2337/db15-0849PMC PMC4764150
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Abstract

Maternal obesity increases the risk for pediatric obesity; however, the molecular mechanisms in human infants remain poorly understood. We hypothesized that mesenchymal stem cells (MSCs) from infants born to obese mothers would demonstrate greater potential for adipogenesis and less potential for myogenesis, driven by differences in β-catenin, a regulator of MSC commitment. MSCs were cultured from the umbilical cords of infants born to normal-weight (prepregnancy [pp] BMI 21.1 ± 0.3 kg/m2; n = 15; NW-MSCs) and obese mothers (ppBMI 34.6 ± 1.0 kg/m2; n = 14; Ob-MSCs). Upon differentiation, Ob-MSCs exhibit evidence of greater adipogenesis (+30% Oil Red O stain [ORO], +50% peroxisome proliferator–activated receptor (PPAR)-γ protein; P < 0.05) compared with NW-MSCs. In undifferentiated cells, total β-catenin protein content was 10% lower and phosphorylated Thr41Ser45/total β-catenin was 25% higher (P < 0.05) in Ob-MSCs versus NW-MSCs (P < 0.05). Coupled with 25% lower inhibitory phosphorylation of GSK-3β in Ob-MSCs (P < 0.05), these data suggest greater β-catenin degradation in Ob-MSCs. Lithium chloride inhibition of GSK-3β increased nuclear β-catenin content and normalized nuclear PPAR-γ in Ob-MSCs. Last, ORO in adipogenic differentiating cells was positively correlated with the percent fat mass in infants (r = 0.475; P < 0.05). These results suggest that altered GSK-3β/β-catenin signaling in MSCs of infants exposed to maternal obesity may have important consequences for MSC lineage commitment, fetal fat accrual, and offspring obesity risk.

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  • Offspring from obese/high-fat diet-fed mothers show increased adiposity and adipocyte hypertrophy postnatally.

    “Offspring from obese/high-fat diet-fed mothers show increased adiposity [88–90] and adipocyte hypertrophy postnatally [89, 91].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [88]

    The Results (Subject Characteristics; page unavailable) report higher percent fat mass at birth in infants of obese mothers than in infants of normal-weight mothers. The paper does not report maternal high-fat-diet exposure or postnatal adipocyte hypertrophy; its cell-culture findings concern adipogenic potential, not measured adipocyte size in offspring. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The differentiation of mesenchymal stem cells to adipocytes in vitro is increased and adiposity is greater in 5-month-old infants from obese mothers.

    “Consistent with this, the differentiation of mesenchymal stem cells to adipocytes in vitro was increased and adiposity greater in 5-month-old infants from obese mothers [88].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [88]

    The Results report greater in-vitro adipogenesis in mesenchymal stem cells from infants of obese mothers and higher infant percent fat mass at birth. The Subjects methods specify that body composition was measured within 72 hours after birth, not at five months; the paper therefore does not support the claim's age qualifier. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Mesenchymal stem cells from infants of obese mothers show a decrease in the abundance of β-catenin, which would favor adipocyte rather than myocyte differentiation.

    “In addition, mesenchymal stem cells from infants of obese mothers showed a decrease in the abundance of β-catenin, which would favor adipocyte rather than myocyte differentiation [88].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [88]

  • There is a positive correlation between the preference of mesenchymal stem cell fate decisions towards the adipocyte lineage and infant adiposity.

    “Previous work has shown there is a positive correlation between the preference of mesenchymal stem cell fate decisions towards the adipocyte lineage and infant adiposity [88, 146].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [88]

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Cited by

Sorted by citations

Authors
Boyle, K. E., Patinkin, Z. W., Shapiro, A. L. B., Baker, P. R., Dabelea, D., & Friedman, J. E.
Affiliations
  • University of Colorado Anschutz (US)
  • Colorado School of Public Health (US)
Corresponding author
Boyle, Kristen E.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2015-12-02
Volume
65
Issue
3
Pages
647-659
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db15-0849
PMC
PMC4764150
OpenAlex
W2186665004
Cited by
115
References
3
Citations by year
2026: 8 · 2025: 12 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 8 · 2020: 12 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 10 · 2015: 1
FWCI
5.78
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/site/license (vor, 274 d)
Locations
  • Diabetes (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Obesity Society (Early Career Research Grant 2013)
  • University of Colorado Center for Women’s Health Research (Junior Faculty Seed Grant)
  • National Cancer Institute (P30/CA046934)
  • National Institute of Child Health and Development (BIRCWH K12/HD057022)
  • American Heart Association (14PRE18230008)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK048520, R01/DK076648)
  • National Center for Advancing Translational Sciences (UL1 TR001082)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
maternal obesity, mesenchymal stem cells, adipogenesis, myogenesis, β-catenin, GSK3β signaling, PPARγ, umbilical cord blood, lineage commitment, lithium chloride
MeSH terms
Glycogen Synthase Kinase 3 beta, Adult, Cell Differentiation, Cells, Cultured, Female, Humans, Longitudinal Studies, Male, Obesity, Pregnancy, Pregnancy Complications, Umbilical Cord, Cohort Studies, Muscle Development, Glycogen Synthase Kinase 3, PPAR gamma, Adipogenesis, beta Catenin, Mesenchymal Stem Cells, Pediatric Obesity

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