Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, USA.
Alcohol Clin Exp Res. 2011 Feb;35(2):229-34. doi: 10.1111/j.1530-0277.2010.01338.x. Epub 2010 Nov 8.
Chronic alcohol consumption is a major factor for several human diseases, and alcoholism is associated with a host of societal problems. One of the major alcohol-induced metabolic changes is the increased NADH levels, which reduces glucose synthesis and increases fatty acid (FA) synthesis. Probably more important is the induction of FA synthesizing enzymes under the control of sterol regulatory element binding proteins (SREBP), plus increased malonyl-CoA, which blocks FA entry to the mitochondria for oxidation. The changes in FA-related lipids, particularly lysophospholipids and ceramides (Cers), in different tissues in ethanol-fed mice have not been reported.
We systematically determined the levels of FA-related lipids, including FAs, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, sphingomyelins, and ceramides (Cers), in the serum and different tissues by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). The study was performed in C57BL/6J mice fed with Lieber-DeCarli diet, in which ethanol was added to account for 27.5% of total calories. The serum and tissues were collected from these mice at the time of killing, and the results were compared to pair-fed controls.
The important observation was that ethanol-induced tissue-specific changes, which were related to different FA chains. Several 22:6 FA, 18:0 FA, 18:0 to 18:3 FA-containing lipids were significantly increased in the serum, liver, and skeletal muscle, respectively. In the kidney, all 22:6 FA-containing lipids detected were increased. In addition, alterations in other lipids in tissues, except adipose tissue, were also observed.
We found tissue-specific alterations in the levels of FA-related lipids after ethanol administration. The implications of these findings pertinent to human physiology/pathology warrant further investigation. More studies are needed to explore the mechanisms on the different effects of ethanol on certain lipids in different tissues.
慢性酒精摄入是多种人类疾病的主要因素，酗酒与许多社会问题有关。酒精引起的主要代谢变化之一是 NADH 水平升高，这会减少葡萄糖合成并增加脂肪酸 (FA) 的合成。也许更重要的是，固醇调节元件结合蛋白 (SREBP) 控制下 FA 合成酶的诱导，以及增加的丙二酰 CoA，它阻止 FA 进入线粒体进行氧化。乙醇喂养小鼠不同组织中与 FA 相关的脂质（特别是溶血磷脂和神经酰胺 (Cers)）的变化尚未报道。
我们通过高效液相色谱-电喷雾串联质谱 (HPLC-ESI-MS/MS) 系统地测定了血清和不同组织中与 FA 相关的脂质，包括 FA、磷脂酰胆碱、磷脂乙醇胺、溶血磷脂酸、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺、溶血磷脂酰肌醇、神经鞘磷脂和神经酰胺 (Cers) 的水平。该研究在喂食 Lieber-DeCarli 饮食的 C57BL/6J 小鼠中进行，其中乙醇占总热量的 27.5%。在处死这些小鼠时收集血清和组织，并将结果与配对喂养的对照组进行比较。
重要的观察结果是，乙醇诱导的组织特异性变化与不同的 FA 链有关。几种 22:6 FA、18:0 FA、18:0 至 18:3 FA 含量的脂质在血清、肝脏和骨骼肌中分别显著增加。在肾脏中，检测到的所有 22:6 FA 含量的脂质都增加了。此外，除脂肪组织外，还观察到组织中其他脂质的变化。
我们发现乙醇给药后 FA 相关脂质的水平存在组织特异性改变。这些发现对人类生理学/病理学的意义值得进一步研究。需要更多的研究来探索乙醇对不同组织中某些脂质产生不同影响的机制。
