低肉碱罗非鱼模型的建立及其能量内稳态调控机制研究

机体能量内稳态（Energy Homeostasis）失衡是造成人类、畜禽和鱼类中各种以脂肪严重沉积为表征的代谢性疾病的重要发生根源，已成为当前营养代谢研究的全球热点。然而，限于鱼类研究模型的缺乏，经济鱼类的能量内稳态调控机制研究至今进展缓慢。本项目将在多年预研基础上，以尼罗罗非鱼活体和细胞为研究对象，在国际上首次构建基于生化抑制的低肉碱经济鱼类模型，并按照动物代谢模型建立的规范要求，完成“确认代谢控制靶点-描述代谢特征-阐明代谢调控机制”三个研究流程。同时，借助代谢示踪、细胞/细胞器孵育、代谢组学和分子调控等现代生物技术，解析体内不同肉碱含量的罗非鱼在脂代谢受阻情况下应对不同能量/营养素摄入的能量内稳态代谢调控和信号调控机制。本项目力图建立一个靶点清晰、表征全面、机制清晰的经济鱼类营养学研究模型，推动经济鱼类能量内稳态调控机制的深入研究，也为养殖鱼类高效饲料配方的理论创新提供新的思路。

The balance of the energy homeostasis is important for the health of organisms, including human, land animals, fish and so on. Now, the impaired energy homeostasis has been regarded as one of the main causes of metabolic syndromes, such as obesity, fatty liver diseases, diabetes, which are mostly characterized with excess lipid deposition. Therefore, energy homeostasis has become a worldwide hot domain in metabolism researches. However, because of the loss of effective animal models, the proceeding of the energy homeostasis study in fish has been blocked for quite long time, thus it is eager to establish an effective fish model for energy homeostasis study. In the present project, the applicant plans to firstly establish low-carnitine tilapia model by using biochemical inhibitor to decrease carnitine content in Nile tilapia or tilapia cells. By following the standard steps in metabolic model establishment, the present project will at first perform “inhibition-rescue” experiments to identify the inhibiting target biochemical reaction in the model fish by independently or jointly using carnitine synthesis inhibitor and/or L/D-carnitine additives. Secondly, the metabolic characteristics of low-carnitine tilapia or tilapia cells will be measured mainly by using metabolomics assay, nutrient metabolism rates assay and molecular measurements for the genes and proteins in nutrient metabolism. Finally, the model fish will be fed with diets containing different energy contents/nutrients composition, and the nutritional physiological functions, nutrient metabolism rates, patch of genes or proteins in nutrients sensing system and the metabolism-related cellular signal pathways will be thoroughly investigated, in order to conclude the energy homeostasis maintaining mechanisms of the model fish when lipid catabolism is lowed. The present project is designed to establish an effective fish model with clear inhibition target, well-known metabolic characteristics and regulatory mechanisms for further energy homeostasis study in fish, and also to provide novel ideas for the theory innovation in the formulation of aquaculture diets.