Division of 'Experimental Obstetrics,' Clinic of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Clinic of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, Berlin, Germany.
Clin Epigenetics. 2018 Oct 24;10(1):131. doi: 10.1186/s13148-018-0567-z.
Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adipose tissue (VAT) as well as blood (cell) samples of GDM-affected (n = 25) vs. matched control (n = 30) mother-child dyads of the prospective "EaCH" cohort study, we addressed whether alterations of adiponectin plasma, mRNA, and DNA methylation levels are associated with GDM and offspring characteristics.
Hypoadiponectinemia was present in women with GDM, even after adjustment for body mass index (BMI). This was accompanied by significantly decreased mRNA levels in both SAT and VAT (P < 0.05), independent of BMI. Maternal plasma adiponectin showed inverse relations with glucose and homeostatic model assessment of insulin resistance (both P < 0.01). In parallel to reduced mRNA expression in GDM, significant (P < 0.05) yet small alterations in locus-specific DNA methylation were observed in maternal fat (~ 2%) and blood cells (~ 1%). While newborn adiponectin levels were similar between groups, DNA methylation in GDM offspring was variously altered (~ 1-4%; P < 0.05).
Reduced adiponectin seems to be a pathogenic co-factor in GDM, even independent of BMI, affecting materno-fetal metabolism. While altered maternal DNA methylation patterns appear rather marginally involved, functional, diagnostic, and/or predictive implications of cord blood DNA methylation should be further evaluated.
脂联素对代谢稳态至关重要，特别是通过胰岛素增敏作用。妊娠糖尿病（GDM）的特征是胰岛素抵抗导致母婴高血糖和不良的出生结局。通过对受影响的 GDM（n=25）与匹配的对照（n=30）母婴对子前瞻性“EaCH”队列研究的配对皮下（SAT）和内脏脂肪组织（VAT）以及血液（细胞）样本进行研究，我们解决了脂联素血浆、mRNA 和 DNA 甲基化水平的改变是否与 GDM 和后代特征相关的问题。
即使在调整体重指数（BMI）后，患有 GDM 的女性也存在低脂联素血症。这伴随着 SAT 和 VAT 中 mRNA 水平显著降低（均 P<0.05），与 BMI 无关。母体血浆脂联素与葡萄糖和稳态模型评估的胰岛素抵抗呈负相关（均 P<0.01）。与 GDM 中 mRNA 表达降低相平行，母体脂肪（约 2%）和血细胞（约 1%）中观察到局部特异性 DNA 甲基化的显著（P<0.05）但微小改变。虽然两组新生儿的脂联素水平相似，但 GDM 后代的 DNA 甲基化发生了不同的改变（约 1-4%；P<0.05）。
即使独立于 BMI，降低的脂联素似乎也是 GDM 的致病协同因子，影响母婴代谢。虽然改变的母体 DNA 甲基化模式似乎涉及较少，但脐带血 DNA 甲基化的功能、诊断和/或预测意义应进一步评估。
