Fishing for new metabolites of omega-3 fatty acids

Fish oil, which is rich in the so-called essential omega-3 fatty acids, is known for its beneficial effects on human health. Adequate intakes of omega-3 fatty acids are known for their positive effects on lipid metabolism and inflammation. The exact mechanisms that explain these effects have been studied for decades, which has shown that omega-3 fatty acids undergo extensive metabolism, leading to the formation of various new lipid metabolites with anti-inflammatory properties. One of these metabolites is docosahexaenoylethanolamide (DHEA). The Nutritional Biology group has been among the first groups to study this metabolite and recognize its importance in the context of nutrition science.

Previous work from our group has shown that 1) DHEA concentrations are increased with higher fish oil intakes and 2) DHEA has anti-inflammatory effects and is more potent compared to its precursor docosahexaenoic acid. Whether DHEA is an ‘metabolic end product’ or whether it can also be further metabolized was not known. Results from previous experiments indicated that DHEA may be a substrate for the cyclooxygenase-2 (COX-2) enzyme, which warranted further exploration of DHEA metabolism.

In this project, the Nutritional Biology group collaborates with the Laboratory of Organic Chemistry. The aim of this project is to explore the COX-2 mediated metabolism of DHEA and to characterize the biological effects of any new metabolites. To fish for these new (and unknown) metabolites, various state-of-the-art techniques are combined, such as high-resolution mass spectrometry and triple quadrupole mass spectrometry. This resulted in the identification of two oxygenated DHEA metabolites, 13-hydroxy-DHEA (13-HDHEA) and 16-HDHEA. These metabolites demonstrate immuno-modulatory properties in vitro with distinct effects on e.g. eicosanoid synthesis compared to their parent DHEA. Current work is aimed at identifying other interaction targets of DHEA.

This project identified and characterized two novel metabolites that are derived from omega-3 fatty acids. Trough this work, we are increasing our understanding of the complexity of omega-3 fatty acid metabolism and how this is related to the health effects of omega-3 fatty acids.