Contributions of intestinal hydrolase and nutrient transporter expression to the postnatal growth in pigs

猪的全身氮利用率在哺乳期较高，约为80%，在断奶过渡期降至60%，在生长-肥育期较低（40-50%）。然而，在组织、器官、细胞和分子水平上，与出生后全身氮利用效率下降相关的生物学机制和因素并不十分清楚。小肠是一个代谢活跃组织，膳食和动脉来源的氨基酸（AA）被肠道广泛利用，用于微生物在管腔和宿主粘膜代谢中的增殖，包括代谢性内源性氮的损失。小肠顶端水解酶和营养转运蛋白在宿主末端营养物质的消化和吸收、保护性解毒以及肠道微生物与宿主之间糖和AA等能量营养物质有效性的分配中发挥重要作用。小肠基底外膜能量营养转运体对肠道和骨骼肌等外周组织之间能量营养物质的分配至关重要。我的长期目标是了解猪出生后小肠水解酶和营养转运蛋白表达变化的机制和相关因素，从而导致猪全身氮利用效率下降。在接下来的五年里，我的具体目标是研究以下方面的产后变化：(1)小肠中主要的根尖膜水解酶基因表达；ii)小肠顶端膜己糖和AA转运体基因的表达；iii)猪小肠基底外侧己糖和AA转运体基因的表达。将使用综合的全身、细胞和分子研究工具来研究靶基因表达，并说明出生后编程和饮食类型的变化如何导致肠道对AA的总体利用增强和全身氮利用效率降低。本研究将提高我们在胃肠道生理学方面的知识，并为改善新生儿生长和猪饲养中氮利用效率提供营养和生物技术策略。

Efficiency of whole body nitrogen (N) utilization is high at about 80% during the suckling, then drops to 60% during the weanling transition and becomes low during the growing-finishing phases (40-50%) in pigs. However, biological mechanisms and factors associated with the postnatal decreases in whole-body efficiency of N utilization are not very clear at the tissue, organ, cellular and molecular levels. The small intestine is a metabolic active tissue and both dietary and arterial sources of amino acids (AA) are extensively utilized by the intestine for microbial multiplication in the lumen and host mucosal metabolism including the metabolic endogenous N losses. Small intestinal apical hydrolases and nutrient transporters play important roles in the host terminal nutrient digestion and absorption, protective detoxification and partitioning of availability of energy nutrients such as sugars and AA between luminal microbes and the host. The small intestinal basolateral membrane energy nutrient transporters are essential to the partitioning of availability of the energy nutrients between the gut and the peripheral tissues such as skeletal muscle. My long-term goal is to understand mechanisms and identify factors associated with the postnatal changes of the small intestinal hydrolase and nutrient transporter expression being for the declining efficiency of whole-body N utilization in the pig. My specific objectives for the next five years are to investigate postnatal changes in i) the major apical membrane hydrolase gene expression in the small intestine; ii) apical membrane hexose and AA transporter gene expression in the small intestine; and iii) basolateral hexose and AA transporter gene expression in the small intestine of pigs. An integrated whole-body, cellular and molecular research tools will be used to study target gene expression and illustrate how postnatal programming and changes of diet types are responsible for an overall enhanced gut utilization of AA and the reduced efficiency of whole body N utilization. The proposed research will improve our knowledge in gastrointestinal physiology and lead to nutritional and biotechnology strategies for improving neonate growth and efficiency of nitrogen utilization in swine feeding.