Abstract
BackgroundThe macrophage plays an important role in innate immunity to induce immune responses. Lipid replacement therapy has been shown to change the lipid compositions of mitochondria and potentially becomes an alternative to reduce the inflammatory response.MethodsWe examined the effects of omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and omega-3 docosahexaenoic acid (DHA) supplementation on the activated the macrophage cell line RAW264.7 via KdO2-lipid A (KLA). The mitochondrial cardiolipin (CL) and monolysocardiolipin (MLCL) were analyzed by LC-MS.ResultsAfter macrophage activation by KLA, CL shifted to saturated species, but did not affect the quantity of CL. Inhibition of delta 6 desaturase also resulted in the same trend of CL species shift. We further examined the changes in CL and MLCL species induced by polyunsaturated fatty acid supplementation during inflammation. After supplementation of AA, EPA and DHA, the MLCL/CL ratio increased significantly in all treatments. The percentages of the long-chain species highly elevated and those of short-chain species reduced in both CL and MLCL.ConclusionsComparisons of AA, EPA and DHA supplementation revealed that the 20-carbon EPA (20:5) and AA (20:4) triggered higher incorporation and CL remodeling efficiency than 22-carbon DHA (22:6). EPA supplementation not only efficiently extended the chain length of CL but also increased the unsaturation of CL.
Highlights
The macrophage plays an important role in innate immunity to induce immune responses
We focused on CL metabolism in KdO2-lipid A (KLA)-activated RAW264.7 cells, combined with the effect of Polyunsaturated fatty acids (PUFAs) supplementation on CL
RAW264.7 cell activation minor changed cardiolipin saturation KLA activates macrophages through Toll-like receptor 4 signaling and triggers the changes of CL saturation, which are critical for the mitochondrial function [25]
Summary
The macrophage plays an important role in innate immunity to induce immune responses. Lipid replacement therapy has been shown to change the lipid compositions of mitochondria and potentially becomes an alternative to reduce the inflammatory response. Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are common supplements in the diet. A plethora of studies have elucidated their roles in anti-inflammation and health benefits [1]. While DHA and EPA are upstream molecules for pre-resolving lipid mediator synthesis, such as resolvins, protectins, and maresins [2], arachidonic acid (AA) is primarily further metabolized into eicosanoids, which are recognized as inflammatory lipid mediators [3]. In CL biosynthesis, phosphatidic acid is metabolized into phosphatidylglycerol that combines with CDP-diacylglycerol by CL synthase to form immature CL, which is further remodeled by transacylase and/or acyltransferase by which various fatty acyl chains are incorporated [8].
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