Gene Expression and DNA Methylation of PPARGC1A in Muscle and Adipose Tissue From Adult Offspring of Women With Diabetes in Pregnancy

Prenatal exposure to maternal hyperglycemia is associated with increased risk of later adverse metabolic health. Changes in regulation of peroxisome proliferator-activated receptor-γ coactivator-1α ( PPARGC1A ) in skeletal muscle and subcutaneous adipose tissue (SAT) is suggested to play a role in developmental programming of dysmetabolism based on studies in human subjects exposed to abnormal intrauterine environment e.g. low birth weight individuals. We studied 206 adult offspring of women with gestational diabetes (O-GDM), type 1 diabetes (O-T1DM) and from the background population (O-BP) including clinical examination, oral glucose tolerance test, gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT. Plasma glucose was significantly higher for both O-GDM and O-T1DM compared to O-BP ( p <0.05). PPARGC1A gene expression in muscle was lower in O-GDM compared to O-BP ( p =0.0003) while no differences were found between O-T1DM and O-BP in either tissue. Muscle and SAT PPARGC1A DNA methylation percentage were similar in all groups. Decreased PPARGC1A gene expression in muscle has previously been associated with abnormal insulin function and may thus contribute to the increased risk of metabolic disease in O-GDM. The unaltered muscle PPARGC1A gene expression in O-T1DM suggests factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM.