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

仔猪的氮素利用率在哺乳期高达80%左右，在断奶过渡期降至60%，在生长育肥期(40%~50%)降低。然而，在组织、器官、细胞和分子水平上，与出生后氮素利用效率下降相关的生物学机制和因素还不是很清楚。小肠是一种代谢活跃的组织，肠道广泛利用膳食和动脉来源的氨基酸(AA)进行肠道微生物繁殖和宿主粘膜代谢，包括代谢内源性N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、保护性解毒以及糖和氨基酸等能量营养物质在管腔微生物和宿主之间的分配中发挥着重要作用。小肠基底膜能量营养转运体在肠道和骨骼肌等外周组织之间的能量营养分配中起着至关重要的作用。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，并找出与之相关的因素，从而导致猪全身氮利用效率的下降。我未来五年的具体目标是研究以下方面的出生后变化：i)主要顶膜水解酶基因在小肠中的表达；ii)顶膜己糖和AA转运体基因在小肠中的表达；以及iii)己糖和AA转运体基因在猪小肠中的表达。综合的全身、细胞和分子研究工具将被用来研究靶基因的表达，并说明出生后编程和饮食类型的改变如何导致AA的肠道利用率全面提高，以及全身N的利用效率降低。这项拟议的研究将提高我们在胃肠道生理学方面的知识，并导致营养和生物技术策略，以改善新生儿的生长和猪饲养中氮的利用效率。

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.