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Background: Exposure to intrauterine obesity can disrupt clock gene rhythmicity in animal models. The aim of this pilot study was to determine if maternal obesity alters rhythmic expression of core clock in mesenchymal stem cells (MSCs) from umbilical cords of human infants born to mothers with obesity (Ob-MSC) vs. normal weight (NW-MSC). Methods: We compared in vitro rhythmic expression patterns of core clock (BMAL1, CLOCK, PER2) and clock-output (NR1D1), components in undifferentiated Ob-MSCs (n = 3) vs. NW-MSCs (n = 3). MSCs were harvested every 2 h, following a dexamethasone shock, for 30 h. Adipogenesis or myogenesis was induced in vitro and markers of adipogenesis and fat storage were assessed, respectively. Results: We detected significant rhythmicity in expression patterns of BMAL1, PER2, and NR1D1 at the group level in Ob- and NW-MSCs (p < 0.05). PER2 oscillatory amplitude was 3-fold higher in Ob-MSCs vs. NW-MSCs (p < 0.006). During adipogenesis, Ob-MSCs had higher PPARγ protein content (p = 0.04) vs. NW-MSC. During myogenesis, Ob-MSCs had higher saturated triacylglycerols (p = 0.04) vs. NW-MSC. Conclusion: Rhythmic expressions of BMAL1, PER2, and NR1D1 are detectable in undifferentiated MSCs. Higher PER2 oscillatory amplitude was paralleled by higher markers of fat storage during differentiation in Ob-MSCs vs. NW-MSCs, and supports that the core clock and cellular metabolism may be linked in infant MSCs. [ABSTRACT FROM AUTHOR]

Objective: In human studies, new model systems are needed for improved mechanistic investigation of developmental predisposition for metabolic disease but also to serve as benchmarks in early life prevention or intervention efforts. In this regard, human infant umbilical cord–derived mesenchymal stem cells (MSCs) are an emerging tool. However, long‐term clinical relevance to in vivo markers of metabolic disease is unknown. Methods: In a cohort of 124 mother/child dyads, this study tested the hypothesis that triglyceride content (TG) of infant MSCs undergoing adipogenesis in vitro (MSC‐TG) is associated with in vivo adiposity (percent fat mass) from birth to early childhood and with fasting glucose and insulin in early childhood. Results: MSC‐TG was positively associated with in vivo child adiposity at birth, age 4 to 6 months, and age 4 to 6 years. MSC‐TG was associated with fasting glucose, but not insulin, at 4 to 6 years. Importantly, MSC‐TG explained an additional 13% variance in child adiposity at 4 to 6 years, after accounting for other established birth predictors (weight and percent fat mass at birth) and other established covariates related to child adiposity (e.g., breastfeeding exposure, physical activity). Conclusions: This work demonstrates the strength of the MSC model for predicting offspring metabolic phenotype into childhood, even when considering the important contribution of other early life risk factors. [ABSTRACT FROM AUTHOR]