DNA methylation and gene expression of TXNIP in adult offspring of women with diabetes in pregnancy
Open Access
- 27 October 2017
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 12 (10), e0187038
- https://doi.org/10.1371/journal.pone.0187038
Abstract
Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action. The extent to which TXNIP DNA methylation levels are decreased and/or gene expression levels increased in SAT or skeletal muscle of a developmentally programmed at-risk population is unknown. The objective of this study was to investigate TXNIP DNA methylation and gene expression in SAT and skeletal muscle, and DNA methylation in blood, from adult offspring of women with gestational diabetes (O-GDM, n = 82) or type 1 diabetes (O-T1DM, n = 67) in pregnancy compared with offspring of women from the background population (O-BP, n = 57). SAT TXNIP DNA methylation was increased (p = 0.032) and gene expression decreased (p = 0.001) in O-GDM, but these differences were attenuated after adjustment for confounders. Neither blood/muscle TXNIP DNA methylation nor muscle gene expression differed between groups. We found no evidence of decreased TXNIP DNA methylation or increased gene expression in metabolic target tissues of offspring exposed to maternal diabetes. Further studies are needed to confirm and understand the paradoxical SAT TXNIP DNA methylation and gene expression changes in O-GDM subjects.This publication has 33 references indexed in Scilit:
- Exposure to Maternal Diabetes in Utero and DNA Methylation Patterns in the OffspringImmunometabolism, 2013
- Hyperglycemia Activates Caspase-1 and TXNIP-Mediated IL-1β Transcription in Human Adipose TissueDiabetes, 2011
- Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin SensitivityDiabetes, 2010
- Epigenetic mechanisms that underpin metabolic and cardiovascular diseasesNature Reviews Endocrinology, 2009
- Thioredoxin‐interacting protein deficiency induces Akt/Bcl‐xL signaling and pancreatic beta‐cell mass and protects against diabetesThe FASEB Journal, 2008
- High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 DiabetesDiabetes Care, 2008
- TXNIP Regulates Peripheral Glucose Metabolism in HumansPLoS Medicine, 2007
- Quantification of mRNA using real-time RT-PCRNature Protocols, 2006
- Hyperglycemia Promotes Oxidative Stress through Inhibition of Thioredoxin Function by Thioredoxin-interacting ProteinOnline Journal of Public Health Informatics, 2004
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002