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Biology 2015, 4(2), 314-326; doi:10.3390/biology4020314

Effect of Different Omega-6/Omega-3 Polyunsaturated Fatty Acid Ratios on the Formation of Monohydroxylated Fatty Acids in THP-1 Derived Macrophages

1
Department of Medicine, Division of Hepatology, Gastroenterology and Endocrinology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin 13353, Germany
2
Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max Delbrueck Center for Molecular Medicine, Berlin 13353, Germany
3
Lipidomix GmbH, Berlin 13125, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Annette Graham
Received: 30 October 2014 / Revised: 28 February 2015 / Accepted: 10 March 2015 / Published: 9 April 2015
(This article belongs to the Special Issue Lipid Metabolism)
View Full-Text   |   Download PDF [121 KB, uploaded 9 April 2015]   |  

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. View Full-Text
Keywords: omega-3; omega-6; LC/ESI-MS/MS; lipid mediators; THP-1 macrophages; 17-HDHA; 18-HEPE; 14-HDHA; HETE; HEPE; HDHA omega-3; omega-6; LC/ESI-MS/MS; lipid mediators; THP-1 macrophages; 17-HDHA; 18-HEPE; 14-HDHA; HETE; HEPE; HDHA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Keeren, K.; Huang, D.; Smyl, C.; Fischer, A.; Rothe, M.; Weylandt, K.-H. Effect of Different Omega-6/Omega-3 Polyunsaturated Fatty Acid Ratios on the Formation of Monohydroxylated Fatty Acids in THP-1 Derived Macrophages. Biology 2015, 4, 314-326.

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