Betaine administration corrects ethanol-induced defective VLDL secretion
Betaine administration corrects ethanol-induced defective VLDL secretion
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DOI：
10.1007/s11010-009-0044-2
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发表时间：
2009-07-01
影响因子：
4.3
通讯作者：
Tuma, Dean J.
中科院分区：
文献类型：
--
作者：
Kharbanda, Kusum K.;Todero, Sandra L.;Tuma, Dean J.
我们以前的研究表明，乙醇诱导的磷脂酰胆碱（PC）合成的改变，通过磷脂酰乙醇胺甲基转移酶（PEMT）途径，暗示缺陷极低密度脂蛋白（VLDL）分泌的肝脂肪变性的发病机制。本研究的目的是确定VLDL分泌是否减少慢性酒精消费和甜菜碱补充，恢复PEMT活性和防止酒精性脂肪变性的发展，可以正常化VLDL分泌。用TritonWR-1339抑制血浆VLDL代谢，测定对照组、乙醇组和甜菜碱组大鼠VLDL分泌。我们观察到与对照组相比，慢性酒精喂养大鼠的VLDL产生率降低。在乙醇饮食中补充甜菜碱增加极低密度脂蛋白的生产率值显着高于对照饮食喂养的大鼠中观察到的。总之，慢性乙醇消耗通过PEMT途径损害PC生成，导致VLDL分泌减少，这有助于肝脂肪变性的发展。通过增加PEMT介导的PC生成，甜菜碱导致肝脏脂肪输出增加，并减弱酒精性脂肪肝的发展。
Our previous studies, demonstrating ethanol-induced alterations in phosphatidylcholine (PC) synthesis via the phosphatidylethanolamine methyltransferase (PEMT) pathway, implicated a defect in very low-density lipoprotein (VLDL) secretion in the pathogenesis of hepatic steatosis. The objective of this study was to determine whether VLDL secretion was reduced by chronic ethanol consumption and whether betaine supplementation, that restores PEMT activity and prevents the development of alcoholic steatosis, could normalize VLDL secretion. The VLDL secretion in rats fed with control, ethanol and the betaine supplemented diets was determined using Triton WR-1339 to inhibit plasma VLDL metabolism. We observed reduced VLDL production rates in chronic alcohol-fed rats compared to control animals. Supplementation of betaine in the ethanol diet increased VLDL production rate to values significantly higher than those observed in the control diet-fed rats. To conclude, chronic ethanol consumption impairs PC generation via the PEMT pathway resulting in diminished VLDL secretion which contributes to the development of hepatic steatosis. By increasing PEMT-mediated PC generation, betaine results in increased fat export from the liver and attenuates the development of alcoholic fatty liver.