Original Article | Published:

Animal Models

Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype

International Journal of Obesity volume 40, pages 17681775 (2016) | Download Citation

Subjects

Abstract

Objective:

Although intrauterine nutritional stress is known to result in offspring obesity and the metabolic phenotype, the underlying cellular/molecular mechanisms remain incompletely understood. We tested the hypothesis that compared with the controls, the bone marrow-derived mesenchymal stem cells (BMSCs) of the intrauterine growth-restricted (IUGR) offspring exhibit a more adipogenic phenotype.

Methods:

A well-established rat model of maternal food restriction (MFR), that is, 50% global caloric restriction during the later-half of pregnancy and ad libitum diet following birth that is known to result in an obese offspring with a metabolic phenotype was used. BMSCs at 3 weeks of age were isolated, and then molecularly and functionally profiled.

Results:

BMSCs of the intrauterine nutritionally-restricted offspring demonstrated an increased proliferation and an enhanced adipogenic molecular profile at miRNA, mRNA and protein levels, with an overall up-regulated PPARγ (miR-30d, miR-103, PPARγ, C/EPBα, ADRP, LPL, SREBP1), but down-regulated Wnt (LRP5, LEF-1, β-catenin, ZNF521 and RUNX2) signaling profile. Following adipogenic induction, compared with the control BMSCs, the already up-regulated adipogenic profile of the MFR BMSCs, showed a further increased adipogenic response.

Conclusions:

Markedly enhanced adipogenic molecular profile and increased cell proliferation of MFR BMSCs suggest a possible novel cellular/mechanistic link between the intrauterine nutritional stress and offspring metabolic phenotype. This provides new potential predictive and therapeutic targets against these conditions in the IUGR offspring.

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Acknowledgements

This research was funded by grants from the NIH (HD058948, HL107118, HD071731, HD127237) and the TRDRP (17RT-0170, and 23RT-0018). The authors had full access to all of the data and take responsibility for the integrity of the data and the accuracy of analysis.

Author contributions

VKR conceived this work. MG, SA, RS, and JL carried out the experiments. VKR, MG, RS, MI analyzed the data. VKR, MG and SA drafted the paper. All authors have the approval of the submitted work.

Author information

Author notes

    • M Gong
    •  & S Antony

    These authors contributed equally to this work

Affiliations

  1. Neonatal Intensive Care Unit, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, Torrance, CA, USA

    • M Gong
    • , S Antony
    • , R Sakurai
    • , J Liu
    • , M Iacovino
    •  & V K Rehan

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to V K Rehan.

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DOI

https://doi.org/10.1038/ijo.2016.157

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