Endocannabinoid-like compounds constitute a group of important signalling lipid molecules widely occurring in nature and involved in diverse pivotal processes. The research within our group in the Division of Human Nutrition focusses mainly on a subgroup of endocannabinoids, the n-PUFA-derived fatty acid amides. Since 2007, we study their role, effects and kinetics on inflammation in relation to disorders with an inflammatory component.
Fatty (acid-) amides are conjugates synthesized from fatty acids and endogenous amines. A renowned representative of this group is the prototypic endocannabinoid anandamide (N-arachidonoyl ethanolamine, AEA) well-known for its pleiotropic effects ranging from energy homeostasis to immune functioning. The n-PUFA-derived fatty acid amide subclass consists out of more than 80 members. Despite this number their potential biological roles have only recently started to be explored. We built evidence that a growing number of members of this subclass display immune-modulating properties. As inflammation plays a pivotal role in the sustainment and possibly the induction of many disorders, this raises perspectives both from a pharmacological and nutritional point of view.
Novel mechanisms underlying the anti-inflammatory activity of omega-3 fatty acids
Here, we investigate the formation, biological activity and kinetics of fatty acid amides that are specifically formed from n-3 LCPUFA. We focus on those which are most relevant from a physiologically and dietary point of view. Recently, we built specific knowledge on the ethanol amide conjugate of DHA, DHEA (N-docosahexaenoylethanolamine). We investigated it’s immune modulating properties (using PBMCs, macrophages, microglial cells and a mice model of colitis), it’s kinetics in mice and human tissue in relation to diet and inflammatory conditions (using LC-MS/MS) and its underlying mechanism of action. Momentarily, we are studying, among others, serotonin- and dopamine conjugates of DHA. We aim to investigate the effects and kinetics of this class of compounds in gastro-intestinal- and neurological disorders, in order to develop novel nutritional and/or pharmacological intervention strategies.
Nutrient sensing in the gastrointestinal tract
Here, we aim to gain more insight in nutrient sensing mechanisms in the gastro-intestinal tract, thereby focussing on gut nutrient sensing receptors and mediators. Gut hormones, like GLP-1, are investigated in relation to appetite control and satiety, thereby including the role of potential novel mediators in the gut, like endocannabinoids, in particular serotonin-conjugates. At first, we have taken an interspecies approach, comparing nutrient sensing receptor expression in different species, like human, pig and mice. Also, underlying mechanisms and mediators are studied in morbidly obese humans subjected to stomach volume reduction surgery. Additionally, the underlying mechanisms of action and effects of sweeteners, in particular of Stevia is researched in models of intestinal entero-endocrine cells and organoids.