Abstract

Gestational diabetes (GDM) is among the most challenging diseases in westernized countries, affecting mother and child, immediately and in later life. Obesity is a major risk factor for GDM. However, the impact visceral obesity and related epigenetics play for GDM etiopathogenesis have hardly been considered so far. Our recent findings within the prospective ‘EaCH’ cohort study of women with GDM or normal glucose tolerance (NGT), showed the role, critical factors of insulin resistance (i.e., adiponectin, insulin receptor) may have for GDM pathophysiology with epigenetically modified expression in subcutaneous (SAT) and visceral (VAT) adipose tissues. Here we investigated the expression and promoter methylation of key inflammatory candidates, tumor necrosis factor-alpha (TNF-α) and suppressor of cytokine signaling 3 (SOCS3) in maternal adipose tissues collected during caesarian section (GDM, n = 19; NGT, n = 22). The mRNA expression of TNF-α and SOCS3 was significantly increased in VAT, but not in SAT, of GDM patients vs. NGT, accompanied by specific alterations of respective promoter methylation patterns. In conclusion, we propose a critical role of VAT and visceral obesity for the pathogenesis of GDM, with epigenetic alterations of the expression of inflammatory factors as a potential factor.

Highlights

  • The growing public health problem stemming from the numerous downstream harmful health conditions link to and brought about by overweight and obesity is an important issue in maternal health

  • In order to contribute to a better understanding of gestational diabetes mellitus (GDM) pathophysiology, we sought to investigate the potential alterations of both TNF-α and/or suppressor of cytokine signaling 3 (SOCS3) mRNA expression and methylation in adipose tissues of women with GDM compared to pregnancies with normal glucose tolerance (NGT)

  • Both groups were categorized as overweight according to the mean prepregnancy BMI (NGT: 26.8 ± 7.9 kg/m2 and GDM: 28.2 ± 6.7 kg/m2)

Read more

Summary

Introduction

The growing public health problem stemming from the numerous downstream harmful health conditions link to and brought about by overweight and obesity is an important issue in maternal health. In order to contribute to a better understanding of GDM pathophysiology, we sought to investigate the potential alterations of both TNF-α and/or SOCS3 mRNA expression and methylation in adipose tissues of women with GDM compared to pregnancies with normal glucose tolerance (NGT). These findings and potential relations were further interrogated with analysis of promoter DNA methylation of both candidates to determine whether this epigenetic modifier influenced/regulated the altered gene expression

Study Cohort
Adipose Tissue Gene Expression Analyses of TNF-α
Adipose Tissue Gene Expression Analyses of SOCS3
Maternal Circulating Plasma TNF-α Levels
DNA Methylation at the TNF-α Promoter in Visceral Adipose Tissue
Subject Data
Maternal Blood and Adipose Tissue Sampling
Maternal Blood TNF-α Analysis
Gene Expression Analyses
DNA Methylation Analyses
Statistical Analyses
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call