Low-density lipoprotein (LDL) cholesterol is the main target of treatment in cardiovascular disease (CVD), but many patients with well-controlled LDL cholesterol can further reduce CVD risk by lowering triglyceride (TG) levels. This can be achieved by omega-3 supplementation; however the mechanism behind this is unknown. This project will investigate if the effects of omega-3 supplementation are conveyed by specific omega-3 derived lipid metabolites, and will involve studies in both mice and humans.
Fishing for novel targets: Omega-3 fatty acid-derived metabolites reduce risk of cardiovascular disease
Omega-3 fatty acids are essential fatty acids. Some effects of omega-3 supplementation are decreased levels of plasma TG (achieved by both decreased lipid synthesis and increased lipid breakdown), and increased levels of anti-inflammatory molecules. Both effects are important in reducing the risk of developing or worsening CVD. The mechanisms behind these effects may be exerted via omega-3 derived metabolites. Uncovering the mechanisms would not only benefit CVD patients, but also patients with other lifestyle diseases with increased plasma TG levels.
The aim of this project is to confirm the suspected effects of omega-3 lipid metabolites on CVD risk factors in an atherosclerosis mouse model, and to translate early findings regarding omega-3 metabolites in mice to humans.
We will increase omega-3 metabolite levels in atherosclerosis-prone Ldlr-/- mice and evaluate if the omega-3 metabolites protect from markers of CVD development (e.g. atherosclerosis development, immune profile, plasma TG levels). In humans, we will administer omega-3 metabolite with a meal, and investigate plasma lipid levels, as well as lipid uptake from the meal. The project will hopefully uncover the potential of omega-3 derived metabolites as an alternative treatment option for CVD patients with increased plasma TG levels, that do not benefit from the therapies available today.
Professor Jens Juul Holst, Department of Biomedical Sciences, University of Copenhagen
Professor Filip K. Knop, Center for Clinical Metabolic Research, Gentofte Hospital
Assistant Professor Trisha J. Grevengoed, Department of Biomedical Sciences, University of Copenhagen