Abstract
Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet not much is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n = 4/group) at the time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations led to identification of indolethylamine N-methyltransferase, tissue factor pathway inhibitor-2, and ephrin type-B receptor 6, not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis as compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity.
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Acknowledgments
The authors receive funding support from the National Institutes of Health (HD063791 to F.H.E. and 1R01AG042188 to G.A.), the Reproductive Scientist Development Program (5K12HD00849 to H.J.H), the March of Dimes Foundation (to H.J.H.) and the Diabetes Research Center at Einstein (DK20541). The supporting institutions had no role in the decision to publish or preparation of the manuscript. We are also grateful to Ana Kaplinski for the organization and to the National institute for Mycoplasma, Soroka University Medical Center, Beer-Sheva, Israel for samples storage.
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Communicated by S. Hohmann.
A. Bashiri, H.J. Heo and F.H. Einstein authors contributed equally.
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Fig. 1s
Scatter plot representing the correlation in gene expression variations in omental and subcutaneous fat from normal weight (x-axis) and obese (y-axis) pregnant women represented in logarithmic scales (PDF 219 kb)
Fig. 2s
Ingenuity Pathway Analysis (IPA) created from all (89 genes) the top candidate most differentially expressed genes (passed multiple comparison analysis) from fat depots of normal weight pregnant women. Gene network association of all that mapped to gene bodies and promoters were analyzed using the “Core Analysis” tool of IPA (PDF 147 kb)
Fig. 3s
Ingenuity Pathway Analysis (IPA) created from all (202 genes) the top candidate most differentially expressed genes (passed multiple comparison analysis) from fat depots of obese pregnant women. Gene network association of all that mapped to gene bodies and promoters were analyzed using the “Core Analysis” tool of IPA.(PDF 68 kb)
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Bashiri, A., Heo, H.J., Ben-Avraham, D. et al. Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat. Mol Genet Genomics 289, 695–705 (2014). https://doi.org/10.1007/s00438-014-0841-5
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DOI: https://doi.org/10.1007/s00438-014-0841-5