Abstract
BackgroundChildren exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation.MethodsDNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts. Glucose tolerance was assessed in all women using an oral glucose tolerance test at the second trimester of pregnancy. Participating women were extensively phenotyped throughout pregnancy, and placenta and cord blood samples were collected at birth.ResultsWe report that maternal glycemia at the second and third trimester of pregnancy are correlated with variations in DNA methylation levels at PRDM16, BMP7, and PPARGC1α and with cord blood leptin levels. Variations in PRDM16 and PPARGC1α DNA methylation levels were also correlated with cord blood leptin levels. Mediation analyses support that DNA methylation variations at the PPARGC1α gene locus explain 0.8 % of the cord blood leptin levels variance independently of maternal fasting glucose levels (p = 0.05).ConclusionsThese results suggest that maternal glucose in pregnancy could produce variations in DNA methylation in BAT-related genes and that some of these DNA methylation marks seem to mediate the impact of maternal glycemia on cord blood leptin levels, an adipokine regulating body weight.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0239-9) contains supplementary material, which is available to authorized users.
Highlights
Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes
Gestational diabetes mellitus (GDM) is a form of diabetes first diagnosed in pregnancy, which affects up to 16 % of pregnant women according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria [8]
In E-21, women with GDM (n = 33) had very similar anthropometric and metabolic profiles on average when compared to the NGT women group, including BMI at the first trimester of pregnancy (25.9 vs. 25.1; p = 0.16)
Summary
Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The lack of thermogenic activation has been associated with obesity in previous animal and human studies [10, 13,14,15,16,17] This has re-established the potential role of BAT in energy balance regulation in adults and suggests that the dysregulation of BAT might be involved in the development of obesity and its associated metabolic disorders [15]. Many gestational events might influence fetal adipogenesis, including BAT and wBAT development [19], but the specific impacts of these events need to be better defined
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