The role of microRNAs in the regulation of inflammation and oxidative stress in monocytes during obesity and associated metabolic disorders.

Obesity is a chronic and complex disorder that is a major contributor to the global burden of disease and morbidity. It leads to the development of hyperglycemia and diabetes, dyslipidemia and hypertension (all components of the metabolic syndrome) and cardiovascular diseases. Blood monocytes and tissue macrophages are culprit cells in the increased inflammatory and oxidative stress state associated with obesity and the onset of obesity-induced metabolic and cardiovascular disorders. The major goal of this project is to better understand the molecular basis of the contribution of inflammation and oxidative stress in the development of these disorders. In detail, we will determine the involvement of regulating microRNAs in the increased inflammatory and oxidative stress state associated with obesity. First, we will use monocyte cell lines to determine their effect on inflammation, oxidative stress and insulin signalling in vitro. Next, we will use transgenic zebrafishes as fas t, low-cost in vivo screening model to validate their effect on macrophage accumulation. Finally, we will use mouse models to establish an active role of the selected microRNAs in the development of obesity, metabolic syndrome and atherosclerosis. Proof of an active role renders them excellent candidates as relevant diagnostic and prognostic markers and targets of intervention.

Keywords:Metabolic syndrome, Obesity, Type 2 diabetes, Cardiovascular diseases, Inflammation, Oxidative stress, microRNA, Biomarker

Disciplines:Cardiac and vascular medicine, Other biological sciences, Endocrinology and metabolic diseases, Immunology