التفاصيل البيبلوغرافية
العنوان: |
Mesenchymal Stem Cells From Infants Born to Obese Mothers Exhibit Greater Potential for Adipogenesis: The Healthy Start BabyBUMP Project. |
المؤلفون: |
Boyle, Kristen E., Patinkin, Zachary W., Shapiro, Allison L. B., Baker II, Peter R., Dabelea, Dana, Friedman, Jacob E., Baker, Peter R 2nd |
المصدر: |
Diabetes; Mar2016, Vol. 65 Issue 3, p647-659, 13p, 2 Charts, 6 Graphs |
مصطلحات موضوعية: |
MESENCHYMAL stem cells, MOTHER-infant relationship, INFANT care, ADIPOGENESIS, MYOGENESIS, HEALTH, PROTEIN metabolism, CELL culture, CELL differentiation, CELL physiology, CONNECTIVE tissue cells, CYTOSKELETAL proteins, LONGITUDINAL method, MUSCULOSKELETAL system, OBESITY, CHILDHOOD obesity, PREGNANCY complications, TRANSFERASES, UMBILICAL cord, PHYSIOLOGY |
مستخلص: |
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/m(2); n = 15; NW-MSCs) and obese mothers (ppBMI 34.6 ± 1.0 kg/m(2); 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. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |