Kinetics and effects of endocannabinoids – analysis of metabolites of n-3 fatty acids

Various molecules in our diet can exert biological effects through specific receptor-mediated mechanisms. Research in our group focusses on the presence and biological properties of metabolites of dietary n-3 fatty acids. To this end, advanced chemical analyses are performed using state-of-the-art equipment to study the presence of endogenous lipid metabolites in a variety of matrices, ranging from cell culture media to human plasma.

Increased intake of n-3 fatty acids has been associated with beneficial effects in brain development, allergies, and cardiovascular and inflammatory diseases. We are investigating the role of the endocannabinoid system as a mediator of the anti-inflammatory effects of n-3 fatty acids. To study this, we develop and improve liquid chromatography coupled to mass spectrometry (LC-MS) based methodology that allows us to investigate the presence of n-3 endocannabinoids and their interaction with other metabolic pathways, such as the oxilipin metabolome.

n-3 endocannabinoids: novel lipids that are present in cells, tissues and plasma

Our work has mainly focused on two n-3 fatty acid N-acyl ethanolamides, docosahexaenoylethanolamide (DHEA) and eicosapentaenoylethanolamide (EPEA). Using LC-MS, we were able to demonstrate the presence of these poorly studied molecules in cell cultures, animal tissues and human plasma. We showed that there is a clear relation between the (dietary) supply of fatty acids and the subsequent profile of endocannabinoids. When n-3 fatty acids are supplied in the diet, higher levels of n-3 endocannabinoids DHEA and EPEA are found in plasma, liver, adipose tissue and the gut. Together with the anti-inflammatory effects observed for DHEA, this work suggests that n-3 endocannabinoids may act as endogenous suppressors of inflammation. Using another LC-MS platform for the quantification of oxylipins, we were able to unravel that DHEA inhibits inflammation by specifically inhibiting the activity of the COX-2 enzyme. Current work is aimed at extending these findings in humans and further exploring which other n-3 lipid metabolites are relevant for inflammation. We collaborate with the Food Chemistry Laboratory at Wageningen University and have ongoing contacts with TNO Zeist.

More research: Effects and kinetics of bioactive lipids in inflammation