linoleic-acid and Endotoxemia

In comparison with dietary high-linoleate safflower oil, high alpha-linolenate perilla oil decreased alkylacyl- and alkenylacyl-glycerophosphocholine (GPC) content in rat kidney by roughly 30 and 25%, respectively. The fatty acid composition was also modified by high alpha-linolenate oil; arachidonic acid (AA) level in alkylacyl-GPC, a platelet-activating factor (PAF) precursor, decreased by 30% along with concomitant increases in the n-3 fatty acid levels. PAF contents under resting conditions were similarly low in the two dietary groups. Fifteen minutes after endotoxin administration, PAF and lyso-PAF contents increased significantly, and the PAF content in the high alpha-linolenate group was 60% lower than in the high linoleate group; the lyso-PAF contents also tended to be lower. Lyso-PAF acetyltransferase and CoA-independent transacylase activities in kidney microsomes increased significantly after endotoxin administration, while PAF acetylhydrolase activity in the cytosol was relatively unchanged. The lyso-PAF acetyltransferase and PAF acetylhydrolase activities did not differ between the two dietary groups, but the CoA-independent transacylase activity was roughly 30% lower in the high alpha-linolenate group. In agreement with in vitro study, our present study demonstrates that dietary high alpha-linolenate suppresses PAF production in rat kidney during systemic endotoxemia, and which is mainly due to the decrease in alkylacyl-GPC content, altered fatty acid compositions of the precursor lipids and lower CoA-independent transacylase activity.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Acetyltransferases; Acyltransferases; alpha-Linolenic Acid; Animals; Dietary Fats; Endotoxemia; Endotoxins; Fatty Acids; Kidney; Linoleic Acid; Male; Phospholipases A; Phospholipids; Platelet Activating Factor; Rats; Rats, Sprague-Dawley

Short-term (i.e., 3 d) continuous enteral feeding of diets containing eicosapentaenoic (EPA) and gamma-linolenic (GLA) polyunsaturated fatty acids (PUFA) to endotoxemic rats reduces the levels of arachidonic acid (AA) and linoleic acid (LA) in alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids with attendant decreases in prostaglandin formation by these cells in vitro. Diets that contain alpha-linolenic acid (LNA) as a substrate for endogenous formation of EPA may not be as effective in facilitating these immune cell modifications given the limited activity of delta6 desaturase. In the present study we compared the effectiveness of an LNA-enriched diet vs. an (EPA + GLA)-enriched diet to displace phospholipid AA from AM and liver K&E cells in vivo in endotoxemic rats fed enterally for 3 or 6 d. We determined the fatty acid composition of AM and K&E cell phospholipids by gas chromatography. We found that AM and K&E cells from rats that had received the EPA + GLA diet for 3 d had significantly (P < 0.001) higher mole percentage of EPA and the GLA metabolite, dihomoGLA, than corresponding cells from rats given the LNA diet or a control diet enriched with LA. Rats given the LNA diet had relatively low levels of stearidonic acid, EPA and other n-3 PUFA, while rats given the LA diet had low levels of GLA and dihomoGLA. We conclude that diets enriched with LNA or LA may not be as effective as those enriched with EPA + GLA for purposes of fostering incorporation of EPA or dihomoGLA into and displacement of AA from macrophage phospholipids under pathophysiologic conditions commonly found in acutely septic patients.

Topics: alpha-Linolenic Acid; Animals; Arachidonic Acid; Dietary Fats, Unsaturated; Eicosapentaenoic Acid; Endothelium; Endotoxemia; gamma-Linolenic Acid; Immune System; Kupffer Cells; Linoleic Acid; Liver; Lung; Macrophages, Alveolar; Male; Rats; Rats, Sprague-Dawley