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

心脏代谢耦合是连接能量代谢和心血管功能的生理过程。这在哺乳动物中是一种公认​​的现象，但在其他脊椎动物中却知之甚少。我的研究计划的长期目标是以鱼为模型来确定参与心脏代谢耦合的细胞机制。表征这些机制将有助于深入了解哺乳动物的核心生理过程和代谢疾病。鱼类是研究这个问题的独特模型，因为它们的自然饮食在物种内和物种之间都不同。这导致膳食多不饱和脂肪酸的成分发生巨大变化，而多不饱和脂肪酸是影响心血管功能的化合物的前体。鱼类栖息的动态环境也会影响它们的新陈代谢，并可能影响心脏代谢耦合。鉴于鱼类的多样性，许多鱼类可能已经进化出了应对代谢/生理紊乱的机制，而这些机制在哺乳动物中可能不起作用。某些毒素的生物活性基于活性氧 (ROS) 代谢的变化。例如，吸入工程纳米颗粒（NP）会导致氧化应激和心血管功能障碍。纳米颗粒具有独特的性质，因此很难根据类似成分的常规化合物的信息来预测其生物活性。纳米粒子可以被细胞吸收，使与能量代谢相关的蛋白质变性并破坏脂质膜。纳米颗粒现在被释放到水生环境中，可以引起鱼类的氧化应激，但它们对心血管的影响尚不清楚。心脏代谢耦合也根源于 ROS 代谢的变化，因此 NP 可能有可能通过多个独立的途径影响这一过程。我将采用多学科方法来实现两个主要研究目标：1）确定动态环境条件下鱼类心脏代谢耦合的细胞机制； 2) 表征纳米颗粒对鱼类能量代谢和心血管功能的影响，旨在确定促进心脏代谢耦合的机制。

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.