TY - JOUR

T1 - Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

AU - Houshmand-Oeregaard, Azadeh

AU - Hansen, Ninna S.

AU - Hjort, Line

AU - Kelstrup, Louise

AU - Broholm, Christa

AU - Mathiesen, Elisabeth R.

AU - Clausen, Tine D.

AU - Damm, Peter

AU - Vaag, Allan

PY - 2017

Y1 - 2017

N2 - Background: Offspring 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). Results: Compared 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. Conclusions: In 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.

AB - Background: Offspring 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). Results: Compared 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. Conclusions: In 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.

KW - Diabetes

KW - Epigenetics

KW - Fetal programming

KW - Gestational diabetes

KW - Methylation

KW - Pregnancy

U2 - 10.1186/s13148-017-0338-2

DO - 10.1186/s13148-017-0338-2

M3 - Journal article

C2 - 28413567

AN - SCOPUS:85018472352

VL - 9

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

SN - 1868-7075

M1 - 37

ER -