Worldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of... Show moreWorldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of preventive and curative strategies for cardiometabolic disease is eagerly warranted. With the studies describes in this thesis, we aimed to disentangle the interwoven physiological, environmental and genetic factors that determine cholesterol and energy metabolism to increase our understanding of their contribution to cardiometabolic disease risk. The first part of this thesis focussed on the cholesteryl ester transfer protein (CETP). The lipid transfer properties of CETP induce a proatherogenic lipoprotein profile. Therefore, CETP inhibitory molecules have been developed and tested in clinical trials for their capability to improve the lipoprotein profile and reduce CVD risk. To fully understand the role of CETP in CVD, its physiology and biological function should be fully unravelled. The focus of the second part of this thesis was on the role of energy metabolism in cardiometabolic health. Specifically, we aimed to study the association of environmental and genetic factors, which were previously described to influence brown adipose tissue (BAT) activity, with energy expenditure and disease outcomes. Show less
Several studies during the past decade have shown that patients with venous thrombosis have an increased risk of subsequent arterial thrombosis, thus suggesting a link between the two diseases. The... Show moreSeveral studies during the past decade have shown that patients with venous thrombosis have an increased risk of subsequent arterial thrombosis, thus suggesting a link between the two diseases. The aim of this thesis was to investigate the associations of traditional cardiometabolic risk factors with risk of a first and recurrent venous thrombosis. We showed that levels of major lipids, i.e. total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides, were not associated with a first venous thrombosis. In contrast, low levels of apolipoproteins B and A1 were associated with an increased risk of a first event. Regarding recurrence, tests for lipid levels, glucose levels and hematologic variables did not identify patients at an increased risk of recurrent venous thrombosis, and these tests should not be done for this indication nor influence decisions on duration of anticoagulant treatment. In this thesis, we further searched for associations between lipids and hemostatic factors, and found that levels of vitamin K-dependent factors (VKDFs), including factor IX, were associated with triglyceride levels. We hypothesized that this association could be explained by common mechanisms, regulating levels of both VKDFs and triglycerides. Show less
