Ethanol-Induced Alterations in Fatty Acid-Related Lipids in Serum and Tissues in Mice

Abstract

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.