Current guidelines barely support marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiology, mainly because results of large trials were equivocal. Most... Show moreCurrent guidelines barely support marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiology, mainly because results of large trials were equivocal. Most large trials have tested EPA alone or EPA + DHA combined as a drug, thereby disregarding the relevance of their blood levels. These levels are frequently assessed with the Omega-3 Index (percentage of EPA + DHA in erythrocytes), which is determined using a specific standardised analytical procedure. EPA and DHA are present in every human being at unpredictable levels (even in the absence of intake), and their bioavailability is complex. Both facts need to be incorporated into trial design and should direct clinical use of EPA and DHA. An Omega-3 Index in the target range of 8-11% is associated with lower total mortality, fewer major adverse cardiac and other cardiovascular events. Moreover, functions of organs such as the brain benefit from an Omega-3 Index in the target range, while untoward effects, such as bleeding or atrial fibrillation, are minimised. In pertinent intervention trials, several organ functions were improved, with improvements correlating with the Omega-3 Index. Thus, the Omega-3 Index is relevant in trial design and clinical medicine, which calls for a widely available standardised analytical procedure and a discussion on possible reimbursement of this test. Show less
In recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This... Show moreIn recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This review presents the most recent insights into how cell intrinsic FA metabolism controls DC and macrophage function, as well as the current evidence of the importance of various exogenous FAs (such as polyunsaturated FAs and their oxidation products-prostaglandins, leukotrienes, and proresolving lipid mediators) in affecting DC and macrophage biology, by modulating their metabolic properties. Finally, we explore whether targeted modulation of FA metabolism of myeloid cells to steer their function could hold promise in therapeutic settings. Show less
The aim of the thesis was to provide more insight into the influence of myocardial steatosis on left ventricular function in healthy volunteers and in patients with type 2 diabetes mellitus.... Show moreThe aim of the thesis was to provide more insight into the influence of myocardial steatosis on left ventricular function in healthy volunteers and in patients with type 2 diabetes mellitus. Therefore we developed a reproducible proton magnetic resonance (MR) spectroscopic technique with respiratory motion compensation to study myocardial steatosis. Using these technique, combined with MR imaging to study myocardial function, correlations between myocardial steatosis and left ventricular function were shown in several (patho)physiological conditions. Furthermore, we showed that myocardial triglyceride content is increased in patients with type 2 diabetes mellitus and is an independent predictor of left ventricular diastolic dysfunction. In addition, differential, tissue-specific partitioning of triglycerides and/or fatty acids among non-adipose organs during various diets was shown. Given the obesity and type 2 diabetes mellitus pandemic and the increasing evidence indicating that lipid oversupply to cardiomyocytes plays a role in the development of diabetic cardiomyopathy, therapeutic strategies that target reduction of cardiac lipid overexposure might be beneficial to prevent diabetic cardiomyopathy. Show less
