Project Details
Projekt
Effects of omega-3 fatty acids on the levels of oxylipins in blood and urine
Subject Area
Nutritional Sciences
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 279364872
Polyunsaturated fatty acids (PUFA) are metabolized in the human metabolism in a complex network of conversion, retroconversion and oxidation. The precursor fatty acids of the omega-6 (n-6) series linoleic acid (LA, C18:2) and the n-3 series alpha-linolenic acid (ALA, C18:3) are transformed in an inefficient enzymatic elongation and desaturation process into the physiologically more active long chain (LC) PUFAs arachidonic acid (AA, C20:4) or eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). In turn, AA, EPA and DHA are converted to oxidized metabolites (oxylipins) by enzymatic catalysis and autoxidation. Many physiologic actions of AA, EPA and DHA are mediated by their oxylipins, which are involved in numerous biological processes as potent lipid mediators. While the class of cyclooxygenase (COX)-mediated AA-metabolites (e.g. 1- and 2-series prostaglandins) have been intensively studies during the last decades, little is known about the novel family of hydroxy-, epoxy- und dihydroxy-FA. Besides autoxidation, these oxylipins are formed in partly multistage conversion processes mediated by i.a. lipoxygenase (LOX), cytochrom P450 monooxygenase (CYP) as well as soluble epoxid hydrolase (sEH).The aim of the project is to systematically investigate the short and long term metabolism of LC n-3 and n-6 PUFA to hydroxy-, epoxy- und dihydroxy-FA in healthy male subjects. Three proof-of-concept studies will be carried out to study the effects of the intake of ALA, EPA and DHA as well as different ALA/LA ratios over a defined period on the levels of free oxylipins (hydroxy-FA, epoxy-FA, dihydroxy-FA as well as several exemplary prostanoids) in plasma and urine. An additional focus will be directed on LC PUFA profiles, which will be measured in different blood fractions (plasma, erythrocyte membranes, free fatty acids, phospholipids).These studies provide knowledge on a) short and long term changes in oxylipin profiles in blood and urine as well as LC PUFA profiles in blood after intake of ALA, EPA, DHA and varying ratios of the n-3/n-6 precursor fatty acids, b) the uptake, bioavailability and distribution of LC PUFA between different blood fractions, c) the conversion and retroconversion of LC PUFA, d) possible circadian fluctuations of oxylipin levels in the blood, and e) oxylipin profiles in blood after ex vivo immune stimulation.
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