PhD ceremony Mr. J.F. de Boer: Novel insights into the pathogenesis of metabolic syndrome-related disease

PhD ceremony: Mr. J.F. de Boer

Dissertation: Novel insights into the pathogenesis of metabolic syndrome-related disease

Promotor(s): prof. U.J.F. Tietge

Faculty: Medical Sciences

Patients with the metabolic syndrome, but also those with type 1 diabetes, have a strong increased risk of cardiovascular disease. The aim of this research project was to provide a better understanding of the pathophysiology leading to insulin resistance and to explore a potential role for altered HDL functionality in diabetes as a contributing factor to increased cardiovascular disease risk.

Data obtained from one study revealed that lack of 12/15-lipoxygenase, especially lack of this enzyme in immune cells, leads to more severe development of diet-induced insulin resistance. Another study showed that mice lacking the enzyme MK2 have a reduced insulin sensitivity, most likely due to decreased expression of an insulin-stimulated glucose transporter. In addition, it was shown that lower HDL levels in type 2 diabetic patients lead to a reduction of the protection against the harmful oxidation of LDL particles, a phenomenon that is strongly linked to the development of atherosclerosis. A study that aimed to investigate the effect of type 1 diabetes on transport of cholesterol from immune cells, via the liver, out of the body, revealed that this so called ‘reverse cholesterol transport pathway’ is impaired in type 1 diabetic conditions. Also, it was found that a recently discovered HDL-associated protein does not impact on the atheroprotective functions of these ‘good’-cholesterol particles although it is preferentially present on these particles in the blood stream.