Department of Obstetrics and Gynecology, The University of British Columbia, Vancouver, British Columbia, Canada.
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
FASEB J. 2023 Nov;37(11):e23200. doi: 10.1096/fj.202301491R.
Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet-induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex-specific effects on offspring pancreas and liver.
流行病学研究报告了怀孕期间叶酸摄入与妊娠糖尿病（GDM）风险之间的关系存在差异。为了开始了解叶酸在怀孕期间如何影响代谢健康，我们确定了过量叶酸补充（推荐量的 5 倍）对母体和胎儿后代代谢健康的影响。使用一种在妊娠期间（西方饮食）和对照小鼠中诱导糖尿病的小鼠（C57BL/6J 雌性）模型，我们表明，叶酸补充改善了喂食西方饮食的雌性小鼠的胰岛素敏感性，并恶化了对照小鼠的胰岛素敏感性。我们在补充叶酸的小鼠的肝脏中未发现未代谢的叶酸，这表明叶酸补充的代谢作用不是由于未代谢的叶酸。来自补充叶酸的母鼠（西方和对照）的雄性胎儿（妊娠第 18.5 天）后代的胰岛细胞质量和密度大于未补充的母鼠的后代；而在雌性后代中则没有观察到这种情况。在补充叶酸的母鼠的胎儿后代中观察到了不同的性别特异性肝基因表达谱，但这在西方饮食和对照组之间有所不同。我们的研究结果表明，叶酸补充会影响雌性小鼠的胰岛素敏感性，但这取决于其代谢表型，并对后代的胰腺和肝脏具有性别特异性影响。
