The aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as... Show moreThe aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as adipokines, inflammation, HDL-cholesterol and postprandial triglyceride response, and cholesteryl ester transfer protein (CETP). We showed that hs-CRP and GlycA as measures of inflammation, adiponectin, and leptin are not associated with clinical and subclinical cardiovascular disease in the general population. However, all may be relevant markers of disease risk. Also, postprandial triglyceride excursions, genetically-determined CETP and HDL-cholesterol, while not related with subclinical atherosclerosis in the general population, may be interesting targets to pursue in women and men separately, and in subgroups of individuals at high-cardiovascular risk. Show less
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
The main objective of this thesis was to study the role of autonomic nervous system (ANS) function in the development of diabetes and cardiovascular disease using an epidemiological approach. Based... Show moreThe main objective of this thesis was to study the role of autonomic nervous system (ANS) function in the development of diabetes and cardiovascular disease using an epidemiological approach. Based on earlier studies it has remained unclear whether impaired ANS function is a risk factor for the development of diabetes and cardiovascular disease, or merely a consequence of pre-existing disease. The main conclusions of this thesis are that excess body fat, in particular visceral fat, is associated with activation of the sympathetic nervous system in individuals without diabetes and cardiovascular disease. Furthermore, this thesis showed that impaired ANS function is not a risk factor for the development of diabetes mellitus. The presented studies suggest that insulin resistance precedes the impairment of the ANS. The results from this thesis also show that impaired ANS function is a risk factor for the development of cardiovascular disease in populations without pre-existing cardiovascular disease. Furthermore, individuals with a higher heart rate have higher concentrations of cholesterol and triglycerides in the circulation and a higher intrahepatic triglyceride content, suggesting that an altered lipid metabolism may be a mechanism underlying the association between ANS function and cardiovascular disease. Show less
