Folate Intake, Mthfr Genotype, and Sex Modulate Choline Metabolism in Mice
Folate Intake, Mthfr Genotype, and Sex Modulate Choline Metabolism in Mice
复制标题
DOI：
10.3945/jn.111.138859
复制
发表时间：
2011-08-01
影响因子：
4.2
通讯作者：
Caudill, Marie A.
中科院分区：
文献类型：
--
作者：
Chew, Tina W.;Jiang, Xinyin;Caudill, Marie A.
胆碱和叶酸在1-碳代谢中相互关联，主要是因为它们作为同型半胱氨酸再甲基化的甲基供体的共同功能。叶酸缺乏和亚甲基四氢叶酸还原酶（MTHFR）的突变降低了主要甲基供体5-甲基四氢叶酸的可用性，这反过来可能导致胆碱代谢的代偿性变化。这项研究调查的假设，减少甲基供应，无论是由于膳食叶酸缺乏或Mthfr基因缺失，将修改组织胆碱代谢的性别特异性的方式。将Mthfr野生型（+/+）或杂合（+/-）敲除小鼠随机分配至叶酸缺乏或对照饮食8周，在此期间，在饮用水中消耗氘标记的胆碱（d9-胆碱）（类似于10 μ mol/d）。Mthfr杂合性没有改变脑胆碱代谢物浓度，但它确实增强了雄性小鼠的胆碱代谢物标记（P < 0.05），并且在雌性小鼠中也有增强的趋势（P < 0.10），这一发现与+/-小鼠脑中饮食胆碱的更大周转一致。饮食中叶酸缺乏的女性产生52%以上（P = 0.027）肝甘油磷酸胆碱，这表明，磷脂酰胆碱（PtdCho）的降解增强。在雌性中，肝脏PtdCho的d3形式标记也减少（P < 0.001），这意味着在叶酸不足的条件下，较少的饮食胆碱衍生的甲基用于从头PtdCho生物合成。男性对叶酸限制的反应是肝胆碱脱氢酶转录物加倍（P < 0.001），这一发现与胆碱向甲基供体甜菜碱的转化增强一致。总的来说，这些数据表明，胆碱代谢的几种适应性变化是由于叶酸代谢的轻微扰动，可能是为了保持甲基的体内平衡。J.营养141：1475-1481，2011.
Choline and folate are interrelated in 1-carbon metabolism, mostly because of their shared function as methyl donors for homocysteine remethylation. Folate deficiency and mutations of methylenetetrahydrofolate reductase (MTHFR) reduce the availability of a major methyl donor, 5-methyltetrahydrofolate, which in turn may lead to compensatory changes in choline metabolism. This study investigated the hypothesis that reductions in methyl group supply, either due to dietary folate deficiency or Mthfr gene deletion, would modify tissue choline metabolism in a sex-specific manner. Mthfr wild type (+/+) or heterozygous (+/-) knockout mice were randomized to a folate-deficient or control diet for 8 wk during which time deuterium-labeled choline (d9-choline) was consumed in the drinking water (similar to 10 mu mol/d). Mthfr heterozygosity did not alter brain choline metabolite concentrations, but it did enhance their labeling in males (P < 0.05) and tended to do so in females (P < 0.10), a finding consistent with greater turnover of dietary choline in brains of +/- mice. Dietary folate deficiency in females yielded 52% higher (P = 0.027) hepatic glycerophosphocholine, which suggests that phosphatidylcholine (PtdCho) degradation was enhanced. Labeling of the hepatic PtdCho in d3 form was also reduced (P < 0.001) in females, which implies that fewer of the dietary choline-derived methyl groups were used for de novo PtdCho biosynthesis under conditions of folate insufficiency. Males responded to folate restriction with a doubling (P < 0.001) of hepatic choline dehydrogenase transcripts, a finding consistent with enhanced conversion of choline to the methyl donor, betaine. Collectively, these data show that several adaptations in choline metabolism transpire as a result of mild perturbations in folate metabolism, presumably to preserve methyl group homeostasis. J. Nutr. 141: 1475-1481, 2011.