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Integrative Biology

Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells

International Journal of Obesity volume 40, pages 1627–1634 (2016)Cite this article

Subjects

Abstract

Background/Objectives:

Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk.

Subjects/Methods:

In this observational cohort study, we recruited 13 lean (pre-pregnancy body mass index (BMI) <25.0 kg m−2) and 24 overweight-obese (‘ov-ob’, BMI⩾25.0 kg m−2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines.

Results:

A total of 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR<0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR<0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in the levels of total free fatty acids (lean: 95.5±37.1 μg ml−1, ov-ob: 124.1±46.0 μg ml−1, P=0.049), palmitate (lean: 34.5±12.7 μg ml−1, ov-ob: 46.3±18.4 μg ml−1, P=0.03) and stearate (lean: 20.8±8.2 μg ml−1, ov-ob: 29.7±17.2 μg ml−1, P=0.04), in infants of overweight-obese mothers.

Conclusions:

Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally programmed differences in oxidative and lipid metabolism.

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Acknowledgements

We are thankful for our research support. SMRC was supported by a Fullbright Fellowship. EI was supported by NICHD K99/R00 Award HD064793. JMD and the Joslin Bioinformatics Core are supported by a Diabetes Research Center (DRC) grant (DK036836). GAPdS was supported by a grant from the National Council of Technological and Scientific Development of Brazil (CNPq 472031/2010). We are grateful for the services of the Vanderbilt Lipid Core.

Author contributions

SMRC designed the study, collected/analyzed the data and reviewed the manuscript; SMRC is the guarantor of the clinical data. EI analyzed the data and wrote the manuscript; EI is the guarantor of transcriptomics and lipidomics analyses. TJM, KH, GD and JMD assisted with the data analysis. GAPdS supervised the clinical study design. M-EP supervised the data analysis and reviewed/edited the manuscript.

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Author notes

  1. S M R Costa and E Isganaitis: These two authors contributed equally to this work.

Authors and Affiliations

  1. Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil

    S M R Costa & G A P da Silva

  2. Research Division, Joslin Diabetes Center, Boston, MA, USA

    S M R Costa, E Isganaitis, T J Matthews, K Hughes, G Daher, J M Dreyfuss & M-E Patti

  3. Harvard Medical School, Boston, MA, USA

    S M R Costa, E Isganaitis & M-E Patti

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  1. S M R Costa
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Correspondence to E Isganaitis.

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Costa, S., Isganaitis, E., Matthews, T. et al. Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells. Int J Obes 40, 1627–1634 (2016). https://doi.org/10.1038/ijo.2016.142

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