动态饲喂色氨酸对哺乳仔猪能量代谢的影响及其作用机制的研究

Insufficiency of energy supplement is one of the factors leading to death and slow growth in neonatal piglets. The requirement of energy shows circadian rhythm in most all of organisms. Tryptophan is the only amino acid showing a circadian rhythm in all three stages of lactation (colostrum, transitional and mature milk). As a metabolite of tryptophan, coenzyme I (NADH/NAD+) shows circadian rhythm activity, but also is involved in the regulation between circadian clock and energy metabolism. Therefore, tryptophan and NAD+ may be the functional substance to regulate energy metabolism and facilitate establishment of circadian clock in the newborn. Until now, acknowledge is poorly understood about the regulation of tryptophan and NAD+ on energy metabolism and circadian rhythm, and effects on performance and development in suckling pigs regulating by dynamic tryptophan. By comprehensive use of various technologies of molecular biology, dynamic nutrition, and genomics, this project will systematically research on effects and mechanisms of dynamic tryptophan supplement on regulation of energy metabolism and development of circadian rhythms in the newborn, using suckling pigs as an animal model, and liver and hypothalamus as subjects. The project is aimed to provide theoretical basis and technical support for dynamic nutrition and metabolism of amino acids, and to establish the scientific and efficient feed formulations, as well as dynamic nutrition regulation programs.

能量供给的不足是导致初生仔猪死亡和生长缓慢的原因之一。几乎所有生物体对能量的需求都具有生物节律性。色氨酸是唯一在哺乳动物各阶段乳汁（初乳、过渡乳和常乳）中均呈现节律性变化的氨基酸。色氨酸的代谢物，辅酶I（NADH/NAD+）是调节生物钟-能量代谢的关键点，在机体内的表达也具有节律性。因此色氨酸和NAD+很可能是调控机体能量代谢、促进新生儿生物钟建立的功能性物质。但是目前关于色氨酸和NAD+对于哺乳仔猪生物钟和能量代谢的机制、以及动态饲喂色氨酸对哺乳仔猪生长和发育的影响知之甚少。本项目综合运用分子生物学、动态营养学和现代组学技术，以哺乳仔猪为动物模型，肝脏和下丘脑为研究对象，探寻动态色氨酸调控新生儿机体能量代谢和生物钟建立的影响。本研究旨在为氨基酸的动态营养和代谢调控作用提供理论依据和技术支撑，同时开发科学高效的猪饲料配方和动态的营养调控方案。

色氨酸是生猪玉米-豆粕型日粮的限制性氨基酸之一。近年来研究发现，除了合成蛋白质之外，色氨酸还是神经递质的前体，参与食欲的调控、消化、胃肠蠕动、昼夜节律、认知和情感反应等生理过程。色氨酸及其代谢物很可能是调控机体能量代谢、促进新生儿生物钟建立的功能性物质。但是目前关于色氨酸及其代谢物对于仔猪生物钟和能量代谢的机制、以及动态饲喂色氨酸对仔猪生长和发育的影响知之甚少。据此，本项目以新生仔猪和生长猪为研究对象，搭建了新生动物自动饲喂平台，运用动物营养学、转录组学和代谢组学手段，对动态饲喂色氨酸对仔猪蛋白质代谢效率、肝脏生理变化和机制进行了系统的研究。发现了早上饲喂高水平色氨酸可以通过促进必需氨基酸的代谢效率促进仔猪对饲料中氮的利用率；此外，妊娠后期母猪日粮动态色氨酸可能通过调节子代肝脏的细胞毒性调控、NADH氧化、ROS代谢等生物过程而对子代健康产生负面影响。本研究为色氨酸在不同阶段生猪饲养阶段的应用提供了理论基础，也为研究新生动物受到外部刺激状态下肝脏和血液的变化提供了新的生物标记物，为研究肝脏和ROS代谢的生物过程变化提供了新的思路。