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Effect of different omega-6/omega-3 polyunsaturated fatty acid ratios on the formation of monohydroxylated fatty acids in THP-1 derived macrophages

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Item Type:Article
Title:Effect of different omega-6/omega-3 polyunsaturated fatty acid ratios on the formation of monohydroxylated fatty acids in THP-1 derived macrophages
Creators Name:Keeren, K. and Huang, D. and Smyl, C. and Fischer, A. and Rothe, M. and Weylandt, K.H.
Abstract:Omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFA) can modulate inflammatory processes. In western diets, the content of n-6 PUFA is much higher than that of n-3 PUFA, which has been suggested to promote a pro-inflammatory phenotype. The aim of this study was to analyze the effect of modulating the n-6/n-3 PUFA ratio on the formation of monohydroxylated fatty acid (HO-FAs) derived from the n-6 PUFA arachidonic acid (AA) and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in THP-1 macrophages by means of LC-MS. Lipid metabolites were measured in THP-1 macrophage cell pellets. The concentration of AA-derived hydroxyeicosatetraenoic acids (HETEs) was not significantly changed when incubated THP-1 macrophages in a high AA/(EPA+DHA) ratio of 19/1 vs. a low ratio AA/(EPA+DHA) of 1/1 (950.6 +/- 110 ng/mg vs. 648.2 +/- 92.4 ng/mg, p = 0.103). Correspondingly, the concentration of EPA-derived hydroxyeicosapentaenoic acids (HEPEs) and DHA-derived hydroxydocosahexaenoic acids (HDHAs) were significantly increased (63.9 +/- 7.8 ng/mg vs. 434.4 +/- 84.3 ng/mg, p = 0.012 and 84.9 +/- 18.3 ng/mg vs. 439.4 +/- 82.7 ng/mg, p = 0.014, respectively). Most notable was the strong increase of 18-hydroxyeicosapentaenoic acid (18-HEPE) formation in THP-1 macrophages, with levels of 170.9 +/- 40.2 ng/mg protein in the high n-3 PUFA treated cells. Thus our data indicate that THP-1 macrophages prominently utilize EPA and DHA for monohydroxylated metabolite formation, in particular 18-HEPE, which has been shown to be released by macrophages to prevent pressure overload-induced maladaptive cardiac remodeling.
Keywords:Omega-3, Omega-6, LC/ESI-MS/MS, Lipid Mediators, THP-1 Macrophages, 17-HDHA, 18-HEPE, 14-HDHA, HETE, HEPE, HDHA, Animals, Mice
Source:Biology
ISSN:2079-7737
Publisher:MDPI (Switzerland)
Volume:4
Number:2
Page Range:314-326
Date:9 April 2015
Official Publication:https://doi.org/10.3390/biology4020314
PubMed:View item in PubMed

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