Insights into the requirement of phosphatidylcholine synthesis for liver function in mice
Insights into the requirement of phosphatidylcholine synthesis for liver function in mice
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DOI：
10.1194/jlr.m300226-jlr200
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发表时间：
2003-10-01
影响因子：
6.5
通讯作者：
Vance, DE
中科院分区：
文献类型：
--
作者：
Noga, AA;Vance, DE
磷脂酰胆碱（PC）在肝脏中通过CDP-胆碱途径和磷脂酰乙醇胺N-甲基转移酶（PEMT）产生，PEMT催化磷脂酰乙醇胺转化为PC。出乎意料的是，肝载脂蛋白B-100分泌在雄性而非雌性Pemt（-/-）小鼠中受到抑制（Noga，A.一、Y. Zhao和D. E.万斯。2002. 277：42358-42365; Noga，A.一、和D. E.万斯。2003. J. Biol. Chem 278：21851-21859）。为了进一步深入了解这一过程，我们比较了喂食食物或高脂肪/高胆固醇（HF/HC）饮食的雄性和雌性小鼠的PC代谢。免疫印迹分析表明，与雄性小鼠相比，雌性小鼠肝脏中存在的PEMT 2是雄性小鼠的两倍。相比之下，来自Pemt（+/+）小鼠肝脏的CTP：磷酸胆碱胞苷酰转移酶的测定表明雄性小鼠比雌性小鼠中的胞苷酰转移酶更活跃。通过在Triton WR 1339存在下向小鼠注射[甲基-H-3]甲硫氨酸，在体内检查PEMT衍生的PC向脂蛋白中的分泌。PEMT衍生的PC转移到较小尺寸的颗粒，以响应HF/HC饮食，但仅在雄性小鼠中。在喂食HF/HC饮食的小鼠中，PEMT衍生的PC向胆汁中的分泌增强。jlr这些结果表明，在小鼠肝脏中通过PEMT途径产生的PC的合成和靶向以性别和饮食特异性方式不同。Noga，A.一、和D. E.万斯。深入了解磷脂酰胆碱合成对小鼠肝功能的需求。J Lipid Res. 2003. 44：1998-2005。
Phosphatidylcholine (PC) is made in the liver by the CDP-choline pathway and via phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the conversion of phosphatidylethanolamine to PC. Unexpectedly, hepatic apolipoprotein B-100 secretion is inhibited in male, but not female, Pemt(-/-) mice (Noga, A. A., Y. Zhao, and D. E. Vance. 2002. J. Biol. Chem. 277: 42358-42365; Noga, A. A., and D. E. Vance. 2003. J. Biol. Chem 278: 21851-21859). To gain further insight into this process, we compared PC metabolism in male and female mice fed chow or a high-fat/high-cholesterol (HF/HC) diet. Immunoblot analyses demonstrated that twice as much PEMT2 was present in livers from female compared with male mice. In contrast, assays of CTP:phosphocholine cytidylyltransferase from livers of Pemt(+/+) mice demonstrated more active cytidylyltransferase in male than in female mice. Secretion of PEMT-derived PC into lipoproteins was examined in vivo by injection of mice with [methyl-H-3]methionine in the presence of Triton WR1339. The PEMT-derived PC shifts to smaller-sized particles in response to a HF/HC diet, but only in male mice. Secretion of PEMT-derived PC into bile was enhanced in mice fed a HF/HC diet. jlr These results demonstrate that the synthesis and targeting of PC produced by the PEMT pathway in the livers of mice differs in a gender-and diet-specific manner.-Noga, A. A., and D. E. Vance. Insights into the requirement of phosphatidylcholine synthesis for liver function in mice. J Lipid Res. 2003. 44:1998-2005.