Coupling cardiovascular control and energy metabolism in fish: the influence of emerging (nanoparticle) toxicants

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Cardiometabolic coupling is the physiological process linking energy metabolism and cardiovascular function. This is a well-established phenomenon in mammals but it is poorly understood in other vertebrates. The long-term goal of my research program is to identify the cellular mechanisms involved in cardiometabolic coupling using fish as a model. Characterizing these mechanisms will provide insight into core physiological processes and metabolic diseases in mammals. Fish are unique models to study this problem as their natural diet differs within and across species. This leads to large variations in the composition of dietary polyunsaturated fatty acids, which are precursors for compounds that influence cardiovascular function. The dynamic environment inhabited by fish also shapes their metabolism and may influence cardiometabolic coupling. Given the diversity of fish species, it is likely that many have evolved mechanisms to cope with metabolic/physiological disturbances that may not be functional in mammals. The bioactivity of certain toxins is based on changes in reactive oxygen species (ROS) metabolism. For example, inhalation of engineered nanoparticles (NPs) leads to oxidative stress and cardiovascular dysfunction. NPs have unique properties which make it difficult to predict their bioactivity based on information for conventional compounds of similar composition. NPs can be taken up by cells, denature proteins related to energy metabolism and damage lipid membranes. NPs are now being released into aquatic environments and can induce oxidative stress in fish but their cardiovascular effects are unknown. Cardiometabolic coupling is also rooted in changes in ROS metabolism so NPs may therefore have the potential to influence this process via multiple, independent pathways. I will use a multidisciplinary approach to address 2 main research objectives:1) identify cellular mechanisms underlying cardiometabolic coupling in fish under dynamic environmental conditions; 2) characterize the influence of NPs on energy metabolism and cardiovascular function in fish with the aim of identifying mechanisms contributing to cardiometabolic coupling.