(Brown) adipose tissue associated metabolic dysfunction and risk of cardiovascular disease in high risk patients

Abstract

In this thesis it was shown that (brown) adipose tissue associated metabolic dysfunction increases the risk on development of cardiovascular disease in high risk patients. Quantity of adipose tissue is an important risk factor for adipose tissue dysfunction but functionality of adipose tissue not solely relies on its quantity. The capacity of adipocytes to expand and safely store nutrients may greatly influence functionality of adipose tissue and cardiovascular risk. Also in normal weight patients whose high risk may go unnoticed. With increasing severity of cardiovascular burden the metabolic consequences of adipose tissue dysfunction become even more important than strict measures of adipose tissue quantity to estimate cardiovascular risk. These findings underline the urge for timely detection of (dys)functional adipose tissue. Functionality of adipose tissue is accompanied by local structural changes in adipose tissue composition which may be quantified using various imaging techniques. We show that Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are able to assess differences in adipose tissue composition that associate with local and systemic consequences of adipose tissue (dys)function. For example, differences in cardiovascular risk factor profile are associated with differences in epicardial adipose tissue composition as measured by CT density in Hounsfield Units. Subsequently, differences in CT density of epicardial adipose tissue are associated with higher scores of coronary artery calcification in men. These findings indicate the potential role for epicardial adipose tissue density as a measure of adipose tissue function in the development of cardiovascular disease. In addition to subcutaneous white adipose tissue (WAT) another type of adipose tissue, named brown adipose tissue (BAT), may exist in humans. BAT is predominantly located within the supraclavicular adipose tissue depot interspersed within WAT cells. BAT is hypothesized to dissipate energy via non-shivering thermogenesis to maintain body temperature during periods of cold and thereby contribute to cardiometabolic health. Due to differences in intracellular water content the Fat signal Fraction of BAT differs from WAT. In thesis we show that MRI reproducibly measures Fat signal Fractions in supraclavicular and subcutaneous adipose tissue. Furthermore, we show that supraclavicular adipose tissue still has BAT characteristics in adult patients with clinical manifest cardiovascular disease and that BAT presence is associated with general measures of obesity and metabolic dysfunction. Findings of this thesis may help to advance our understanding of adipose tissue associated metabolic (dys)function in the development and risk assessment of cadiovascular disease. Longitudinal and experimental studies are recommended to further elucidate mechanisms underlying imaging of adipose tissue composition and to assess whether imaging of adipose tissue composition is able to longitudinal determine cardiovascular disease risk.