Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.
Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.
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DOI：
10.1016/j.jnutbio.2017.08.004
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Nam J;Greenwald E;Jack-Roberts C;Ajeeb TT;Malysheva OV;Caudill MA;Axen K;Saxena A;Semernina E;Nanobashvili K;Jiang X
母体肥胖增加了大量营养素的胎盘运输，导致胎儿过度生长和以后的肥胖。胆碱参与脂肪酸代谢，作为甲基供体，并影响生长信号，这可能会改变胎盘大量营养素的稳态，影响胎儿的生长。使用母体肥胖的小鼠模型，我们评估了母体补充胆碱对预防胎儿过度生长和恢复胎盘大量营养素稳态的作用。从交配前4周开始至妊娠第12.5天，分别向C57 BL/6 J小鼠喂食高脂肪（HF，60% kcal来自脂肪）饮食或正常（NF，10% kcal来自脂肪）饮食，并饮用25 mM氯化胆碱或对照纯化水。测量胎儿和胎盘重量、代谢物和基因表达。HF喂养显著（P < 0.05）增加HF对照（HFCO）与NF对照（NFCO）动物的胎盘和胎儿重量，而HF胆碱补充（HFCS）组有效地使胎盘和胎儿重量正常化至NFCO组的水平。与HFCO组相比，HFCS组胎盘中葡萄糖转运蛋白1（GLUT 1）和脂肪酸转运蛋白1（FATP 1）的表达降低（P < 0.05），糖原累积减少。HFCS组的胎盘4 E结合蛋白1和核糖体蛋白s6磷酸化水平也较低（P < 0.05），这是雷帕霉素复合物1（mTORC 1）激活机制靶点的指标，有利于大量营养素的补充。总之，我们的研究结果表明，母体胆碱补充剂预防了妊娠中期肥胖小鼠的胎儿过度生长，并改善了胎盘大量营养素稳态的生物标志物。
Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor, and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites, and gene expression were measured. HF feeding significantly (P < 0.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P < 0.05) glucose transporter 1 (GLUT1) and fatty acid transport protein 1 (FATP1) expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P < 0.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 (mTORC1) activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at mid-gestation and improved biomarkers of placental macronutrient homeostasis.
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