Lisanne Blauw, BSc

The worldwide prevalence of obesity is rapidly increasing and obesity-associated disorders, including diabetes and cardiovascular disease, are becoming global health problems. The Netherlands Epidemiology of Obesity (NEO) study is a prospective cohort study, designed to investigate pathways that lead to obesity-related diseases. This large, population-based cohort includes 6,671 individuals aged between 45 and 65 years, with an oversampling of individuals with overweight or obesity. As a NEO study PhD student my research is two-sided. I focus on the role of cholesteryl ester transfer protein (CETP) in cardiovascular disease, and on the association of obesity-associated gene variants with resting energy expenditure.

CETP circulates in the blood and contributes to an atherogenic lipoprotein profile. As CETP is associated with increased cardiovascular disease risk, a reduction in CETP activity has been proposed as a strategy to improve the lipoprotein profile and reduce cardiovascular disease. However, in light of the termination of the clinical trials with the CETP inhibitors dalcetrapib and evacetrapib, we have to reconsider the role of CETP in cardiovascular disease risk. My PhD project is therefore focused on studying the determinants of, and factors depending on serum CETP concentration, to further understand the role of CETP in cardiovascular disease.

Environmental factors play a major role in the onset of obesity, and lifestyle interventions are therefore the keystones of treatment and prevention. However, because 40-70% of the inter-individual differences in obesity risk in the general population are explained by genetics, it is of great interest for future intervention strategies to unravel genetic factors and related biological pathways involved in obesity. A possible underlying pathway in the association between genetic variation and obesity is activation of brown adipose tissue. Brown fat combusts lipids to generate heat, thereby increasing energy expenditure via increased fat oxidation. We aim to elucidate the influence of genetic variation on obesity risk via resting energy expenditure and fat oxidation. In the NEO study, I will study the association between variation in obesity-related genes and measures of resting energy expenditure and substrate oxidation.