Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

Abstract

BackgroundOffspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription.We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57).ResultsCompared to O-BP, we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene expression of all adipokines in O-GDM, decreased RETN expression in O-T1DM, and increased LEP and ADIPOQ methylation in O-GDM. In multivariate regression analysis, O-GDM remained associated with increased ADIPOQ methylation and decreased ADIPOQ and RETN gene expression and O-T1DM remained associated with decreased RETN expression after adjustment for potential confounders and mediators.ConclusionsIn conclusion, offspring of women with diabetes in pregnancy exhibit increased ADIPOQ DNA methylation and decreased ADIPOQ and RETN gene expression in SAT. However, altered methylation and expression levels were not reflected in plasma protein levels, and the functional implications of these findings remain uncertain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0338-2) contains supplementary material, which is available to authorized users.

Alterations of adiponectin gene expression and DNA methylation in adipose tissues and blood cells are associated with gestational diabetes and neonatal outcome

“…Nevertheless, we cannot exclude that this finding has no decisive functional implications for the offspring, as CB adiponectin was not significantly altered in GDM offspring, and apparently, blood cells did not reflect maternal adipose tissue methylation. Interestingly and worth noting, however, a very recent study in adults born to mothers with GDM is showing significantly increased ADIPOQ DNA methylation, accompanied with lower gene expression in SAT [ 34 ].…”

Diabetes in pregnancy: a new decade of challenges ahead

“…However, to date, genetic risk scores, derived from known diabetes-associated gene polymorphisms, have not meaningfully contributed to GDM prediction. Epigenetic changes have been proposed to be involved in the effects of in utero exposure to maternal hyperglycaemia on long-term metabolic health issues of the offspring [ 69 ]. An example of success using whole-transcriptome analysis comes from a study that showed marked upregulation of tryptophan hydroxylase-1 in islets of pregnant mice [ 70 ].…”

DNA methylation and gene expression of TXNIP in adult offspring of women with diabetes in pregnancy

“…The current study is the second follow-up in an observational study of a birth cohort exposed to diabetes in pregnancy. Material from the same cohort has been used previously, and study design, inclusion criteria and baseline data have been described in detail elsewhere [ 1 , 2 , 24 , 25 ]. The participants were adult offspring of women with either gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, and a randomly selected control group consisting of offspring of women from the background population (O-BP, N = 57).…”

“…Of these 254 belonged to a group that was not re-invited for the second follow-up, leaving a total of 812 potentially eligible offspring in the original cohort, 597 of whom participated in the first cross-sectional follow-up study in 2003–2005 [ 1 , 2 , 24 ]. Of these, 456 participants were eligible for participation in the second follow-up, and 250 were lost or excluded for various reasons, resulting in a total of 206 participants (25% of the original cohort or 45% from the first follow-up in the current study as previously described [ 24 , 25 ] ( Fig 1 ).…”