title: Gene Expression and DNA Methylation of PPARGC1A in Muscle and Adipose Tissue From Adult Offspring of Women With Diabetes in Pregnancy.
abstract: Prenatal exposure to maternal hyperglycemia is associated with an increased risk of later adverse metabolic health. Changes in the 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 the developmental programming of dysmetabolism based on studies of human subjects exposed to an abnormal intrauterine environment (e.g., individuals with a low birth weight). We studied 206 adult offspring of women with gestational diabetes mellitus (O-GDM) or type 1 diabetes (O-T1D) and of women from the background population (O-BP) using a clinical examination, oral glucose tolerance test, and gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT. Plasma glucose was significantly higher for both O-GDM and O-T1D compared with O-BP (P < 0.05). PPARGC1A gene expression in muscle was lower in O-GDM compared with O-BP (P = 0.0003), whereas no differences were found between O-T1D and O-BP in either tissue. PPARGC1A DNA methylation percentages in muscle and SAT were similar among 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 PPARGC1A gene expression in muscle of O-T1D suggests that factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM.
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark louisekelstrup@dadlnet.dk line.hjort@regionh.dk.
authors.forename: Louise
authors.initials: L
authors.lastname: Kelstrup
authors.affiliation: Diabetes and Metabolism Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark louisekelstrup@dadlnet.dk line.hjort@regionh.dk.
authors.forename: Line
authors.initials: L
authors.lastname: Hjort
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark Diabetes and Metabolism Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Houshmand-Oeregaard
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Obstetrics and Gynecology, Hilleroed Hospital, University of Copenhagen, Hilleroed, Denmark.
authors.forename: Tine D
authors.initials: TD
authors.lastname: Clausen
authors.affiliation: Diabetes and Metabolism Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ninna S
authors.initials: NS
authors.lastname: Hansen
authors.affiliation: Diabetes and Metabolism Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christa
authors.initials: C
authors.lastname: Broholm
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Liv
authors.initials: L
authors.lastname: Borch-Johnsen
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.affiliation: Diabetes and Metabolism Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan A
authors.initials: AA
authors.lastname: Vaag
authors.affiliation: Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D019175:DNA Methylation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha