Obesity constitutes a major health problem, firstly due to the increasing prevalence and secondly because of its associated morbidity. Besides high caloric diet and lack of physical activity, exposure to pesticides and endocrine disrupting pollutants is now suspected to be an obesogenic factor.
Recently, a strong association was found between a specific paraoxonase 1 (PON1) genotype, pesticide exposure and adverse epigenetic (re)programming of endocrine pathways in patients with obesity. PON enzymes metabolize several pesticides and a decrease in PON1 expression promotes adverse lipid metabolism. Given the crucial role of PON members in protecting from adverse environmental exposure and from obesity, there is an urgent need for further research on the underlying mechanisms of exposure-related obesity. In this project, a zebrafish model for obesity in humans will be induced by overfeeding using a high-fat diet.
This model will be used to study the role of PON(1-3) in the relation between exposure to pollutants and obesity, including (epi)genetic regulation mechanisms. Suspected obesogenic pollutants include polychlorobiphenyls (PCBs) which were widely used in the past (e.g. as coolant fluids) and now still persist in the environment, organochlorine pesticides, phthalates that are added to plastics to increase flexibility and bisphenol A used for the production of plastics. Zebrafish will be exposed to known or suspected obesogenic pollutants and the impact on the development of obesity will be studied. To this end, measures of physiological performance (e.g., BMI, swimming performance, reproductive capacity), tissue function (e.g., lipid accumulation, cholesterol levels) as well as molecular mechanisms (e.g., transcriptomics, epigenomics) will be studied. Finally, the impact of therapeutical interventions (e.g., swimming exercises using swim tunnels) will be assessed.