Wang Junjun, Chen Lixiang, Li Peng, Li Xilong, Zhou Huaijun, Wang Fenglai, Li Defa, Yin Yulong, Wu Guoyao
State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
J Nutr. 2008 Jun;138(6):1025-32. doi: 10.1093/jn/138.6.1025.
Dietary supplementation of glutamine prevents intestinal dysfunction and atrophy in weanling piglets, but the underlying mechanism(s) are largely unknown. This study was conducted to test the hypothesis that weaning or glutamine may modulate expression of genes that are crucial for intestinal metabolism and function. In Expt. 1, we obtained small intestine from 28-d-old pigs weaned at 21 d of age and from age-matched suckling piglets. In Expt. 2, piglets were weaned at 21 d of age and then had free access to diets supplemented with 1% L-glutamine (wt:wt) or isonitrogenous L-alanine (control). At d 28, we collected small intestine for biochemical and morphological measurements and microarray analysis of gene expression using the Operon Porcine Genome Oligo set. Early weaning resulted in increased (52-346%) expression of genes related to oxidative stress and immune activation but decreased (35-77%) expression of genes related to macronutrient metabolism and cell proliferation in the gut. Dietary glutamine supplementation increased intestinal expression (120-124%) of genes that are necessary for cell growth and removal of oxidants, while reducing (34-75%) expression of genes that promote oxidative stress and immune activation. Functionally, the glutamine treatment enhanced intestinal oxidative-defense capacity (indicated by a 29% increase in glutathione concentration), prevented jejunal atrophy, and promoted small intestine growth (+12%) and body weight gain (+19%) in weaned piglets. These findings reveal coordinate alterations of gene expression in response to weaning and aid in providing molecular mechanisms for the beneficial effect of dietary glutamine supplementation to improve nutrition status in young mammals.
日粮补充谷氨酰胺可预防断奶仔猪肠道功能障碍和萎缩，但其潜在机制尚不清楚。本研究旨在验证断奶或谷氨酰胺可能调节对肠道代谢和功能至关重要的基因表达这一假设。在实验1中，我们从21日龄断奶的28日龄仔猪和年龄匹配的哺乳仔猪获取小肠。在实验2中，仔猪在21日龄断奶，然后自由采食补充1% L-谷氨酰胺（重量比）或等氮L-丙氨酸（对照）的日粮。在第28天，我们收集小肠进行生化和形态学测量，并使用Operon猪基因组寡核苷酸芯片进行基因表达微阵列分析。早期断奶导致与氧化应激和免疫激活相关的基因表达增加（52%-346%），但与肠道中常量营养素代谢和细胞增殖相关的基因表达减少（35%-77%）。日粮补充谷氨酰胺可增加细胞生长和清除氧化剂所需基因的肠道表达（120%-124%），同时降低促进氧化应激和免疫激活的基因表达（34%-75%）。在功能上，谷氨酰胺处理增强了肠道氧化防御能力（谷胱甘肽浓度增加29%表明），预防空肠萎缩，并促进断奶仔猪小肠生长（+12%）和体重增加（+19%）。这些发现揭示了断奶后基因表达的协同变化，并有助于为日粮补充谷氨酰胺改善幼龄哺乳动物营养状况的有益作用提供分子机制。
