Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5 (n-3)) inhibit T lymphocyte activation probably by displacing acylated signaling proteins from membrane lipid rafts. Under physiological conditions, saturated fatty acyl residues of such proteins partition into the cytoplasmic membrane lipid leaflet with high affinity for rafts that are enriched in saturated fatty acyl-containing lipids. However, the biochemical alteration causing displacement of acylated proteins from rafts in PUFA-treated T cells is still under debate but could principally be attributed to altered protein acylation or changes in raft lipid composition. We show that treatment of Jurkat T cells with polyunsaturated eicosapentaenoic acid (20:5 (n-3)) results in marked enrichment of PUFAs (20:5; 22:5) in lipids from isolated rafts. Moreover, PUFAs were significantly incorporated into phosphatidylethanolamine that predominantly resides in the cytoplasmic membrane lipid leaflet. Notably, palmitate-labeled Src family kinase Lck and the linker for activation of T cells (LAT) were both displaced from lipid rafts indicating that acylation by PUFAs is not required for protein displacement from rafts in PUFA-treated T cells. In conclusion, these data provide strong evidence that displacement of acylated proteins from rafts in PUFA-treated T cells is predominantly due to altered raft lipid composition.
"This indicates that, at the sn-1 position of phospholipids, a 18:1 fatty acid is not, while a 16:0 or 18:0 fatty acid is, favorable for inclusion in DRMs. The data of Stulnig et al. (2001) show a similar enrichment of 16:0 and 18:0 fatty acids in the DRM fraction of Jurkat T cells, while 16:1 and 18:1 fatty acids were excluded from DRMs. Unfortunately, the position of the fatty acids was not determined. "
[Show abstract][Hide abstract] ABSTRACT: Lipid rafts are micro-domains of ordered lipids (L o phase) in biological membranes. The L o phase of cellular membranes can be isolated from disordered lipids (L d phase) after treatment with 1 % Triton X-100 at 4 °C in which the L o phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and por-cine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with<5 mM methyl-ß-cy-clodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein–cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the L o phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context.
Cell and Tissue Research 09/2015; DOI:10.1007/s00441-015-2272-y · 3.57 Impact Factor
"One recent in vivo study demonstrated that a small fraction of n-3 PUFAs from dietary fish oil incorporated into sphingolipids of murine B cells (Rockett et al., 2012). These results were consistent with similar findings in cell culture with immortal T cells (Stulnig et al., 2001). A fourth possibility we propose is that n-3 PUFA acyl chains could become esterified to cholesterol to modify Figure 2 Potential mechanisms by which n-3 PUFAs could disrupt lipid microdomain distribution. "
"NADPH oxidase induces ROS production, which is found to be necessary for TLR-4 signalling
. In addition, the incorporation of DHA into lipid membrane disrupts the translocation of TLR-4 into lipid raft, thus inhibiting the TLR-4 signalling pathway
[50,55]. The disrupted TLR-4 signalling pathways lead to the inhibition of NF-κB thus resulting in the downregulation of inflammatory responses
[Show abstract][Hide abstract] ABSTRACT: Obesity plays a pivotal role in the development of low-grade inflammation. Dietary fatty acids are important modulators of inflammatory responses. Saturated fatty acids (SFA) and n-6 polyunsaturated fatty acids (PUFA) have been reported to exert pro-inflammatory effects. n-3 PUFA in particular, possess anti-inflammatory properties. Numerous clinical studies have been conducted over decades to investigate the impact of dietary fatty acids on inflammatory response in obese individuals, however the findings remained uncertain. High fat meals have been reported to increase pro-inflammatory responses, however there is limited evidence to support the role of individual dietary fatty acids in a postprandial state. Evidence in chronic studies is contradictory, the effects of individual dietary fatty acids deserves further attention. Weight loss rather than n-3 PUFA supplementation may play a more prominent role in alleviating low grade inflammation. In this context, the present review provides an update on the mechanistic insight and the influence of dietary fats on low grade inflammation, based on clinical evidence from acute and chronic clinical studies in obese and overweight individuals.
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