Maternal obesity disrupts the methionine cycle in baboon pregnancy.
Maternal obesity disrupts the methionine cycle in baboon pregnancy.
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DOI：
10.14814/phy2.12564
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发表时间：
2015-11
影响因子：
2.5
通讯作者：
Caudill MA
中科院分区：
文献类型：
--
作者：
Nathanielsz PW;Yan J;Green R;Nijland M;Miller JW;Wu G;McDonald TJ;Caudill MA
母亲在怀孕期间摄入膳食甲基微量营养素（例如叶酸、胆碱、甜菜碱和维生素 B-12）对于母亲和胎儿正常的蛋氨酸代谢至关重要，并且对于重要的代谢过程（包括参与发育规划的代谢过程）至关重要。怀孕期间母亲肥胖和营养过剩会影响发育规划，可能使成年后代容易出现各种慢性健康问题。在本研究中，我们假设母亲肥胖会失调母亲和胎儿的蛋氨酸循环。为了检验这一假设，我们开发了一个在妊娠前和妊娠期间饲喂高脂肪、高能量饮食 (HF-HED) 的未产狒狒肥胖模型，并检查了蛋氨酸循环生物标志物（例如同型半胱氨酸、蛋氨酸、胆碱、甜菜碱、关键氨基酸、叶酸和维生素 B-12 的循环浓度）。动物被分组饲养，允许充分的身体活动和社会互动。对照组母亲孕前体脂百分比为 5%，HF-HED 母亲为 19%，而 HF-HED 母亲的足月胎儿体重降低了 16%。 HF-HED 组的母体和胎儿同型半胱氨酸较高，而母体和胎儿维生素 B-12 和甜菜碱较低。 HF-HED 组中母体循环叶酸明显升高，表明母体维生素 B-12 消耗导致叶酸代谢受损（甲基陷阱）。最后，HF-HED 胎儿的胎儿蛋氨酸、甘氨酸、丝氨酸和牛磺酸较低。这些数据表明，母体肥胖扰乱了灵长类动物妊娠中的蛋氨酸循环，为肥胖孕妇中观察到的表观遗传变化提供了一种机制，并为人类妊娠并发肥胖症提供了诊断和治疗的机会。
Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized that maternal obesity would dysregulate the maternal and fetal methionine cycle. To test this hypothesis, we developed a nulliparous baboon obesity model fed a high fat, high energy diet (HF-HED) prior to and during gestation, and examined methionine cycle biomarkers (e.g., circulating concentrations of homocysteine, methionine, choline, betaine, key amino acids, folate, and vitamin B-12). Animals were group housed allowing full physical activity and social interaction. Maternal prepregnancy percent body fat was 5% in controls and 19% in HF-HED mothers, while fetal weight was 16% lower in offspring of HF-HED mothers at term. Maternal and fetal homocysteine were higher, while maternal and fetal vitamin B-12 and betaine were lower in the HF-HED group. Elevations in circulating maternal folate were evident in the HF-HED group indicating impaired folate metabolism (methyl-trap) as a consequence of maternal vitamin B-12 depletion. Finally, fetal methionine, glycine, serine, and taurine were lower in the HF-HED fetuses. These data show that maternal obesity disturbs the methionine cycle in primate pregnancy, providing a mechanism for the epigenetic changes observed among obese pregnant women and suggesting diagnostic and therapeutic opportunities in human pregnancies complicated by obesity.