早期断奶仔猪血清代谢组学研究及谷氨酰胺对日粮消化吸收和代谢的影响
|
摘要
现代化养殖中通常对仔猪采取早期断奶以提高整个猪场的生产效率,而早期断奶产生的应激对仔猪的生长代谢产生严重影响。本论文在采用代谢组学方法分析仔猪早期断奶过程中血清氨基酸代谢谱变化的基础上,研究谷氨酰胺对仔猪肠道消化吸收功能和机体代谢的影响,并用体外细胞模型探讨了谷氨酰胺抑制肠道上皮氧化凋亡的机理。主要试验设计及研究结果如下：
试验一：本试验的主要目的是分析仔猪早期断奶过程中血清氨基酸代谢谱的动态变化。选取8头21日龄断奶仔猪,在断奶后0、1、3、5、7、10、15、30d采集血液样本用于氨基酸分析。试验结果显示,血清精氨酸与其直接的前体物质瓜氨酸和鸟氨酸含量在断奶后1～5d内显著下降(P<0.05),在断奶后7-30d上升。亮氨酸、脯氨酸、酪氨酸和牛磺酸在断奶后1～3d内显著下降(P<0.05),然后其含量上升。异亮氨酸、赖氨酸、甘氨酸和丝氨酸含量在断奶后5d显著低于其他时间点的含量,然后在断奶后7-30d上升。蛋氨酸含量在断奶后0-3d内变化较小(P>0.05),在断奶后5d,其含量分别比断奶后0d、1d和3d增加了41.61%(P<0.05)、43.51%(P<0.05)和41.11%(P<0.05),之后保持稳定。血清苏氨酸含量在断奶后3d比断奶后O d和1d分别增加了31.67%(P<0.05)和79.06%(P<0.05),断奶后10d其达到最大值,在断奶后15d和30d其含量显著降低。谷氨酸含量(包括谷氨酸+谷氨酰胺)在断奶后0d、1d和10d显著低于其他时间段含量(P<0.05)。总氨基酸含量在断奶后0d显著高于断奶后各时间段总氨基酸含量(P<0.05),在断奶后1-5d,总氨基酸含量逐渐降低,断奶后7d起升高并至断奶后30d无显著变化(P>0.05)。主成分分析得分图显示,随着断奶后时间的延长,血清氨基酸代谢谱与断奶后O d的代谢谱差异逐渐变大,然后逐渐向断奶后0d代谢谱位置靠拢,并趋于稳定,其中断后3-5d血清氨基酸代谢谱变化幅度最大。偏最小二乘法判别分析模型显示,谷氨酰胺和谷氨酸为在NRC(1998)饲养标准下区分断奶后各时间点血清代谢谱最重要的氨基酸。
试验二：基于气相色谱/质谱联用技术的代谢组学方法运用于研究仔猪早期断奶与饲粮中补充L-谷氨酰胺(Gln)对血清代谢物的影响。将36头21日龄仔猪随机分成三组,一组继续哺乳(哺乳组),另外两组仔猪进行断奶处理,分别在其日粮中添加1%Gln或等氮的L-丙氨酸(Ala),即为Gln组与对照组。处理7d后采集血清样本进行研究。结果显示,与哺乳组相比,对照组仔猪中有20种代谢物含量显著下降(P<0.05)。这些数据结合KEGG数据库代谢通路分析表明,早期断奶引起广泛的代谢改变,包括精氨酸和脯氨酸代谢、氨基糖和核苷酸代谢、乳糖代谢、甘油磷酸酯代谢、不饱和脂肪酸的生物合成和脂肪酸代谢。饲粮添加Gln能提高仔猪血清肌酐、D-木糖、2-羟丁酸、反式-9-十六烯酸、α-L-呋喃半乳糖含量(P<0.05)。这些物质涉及精氨酸和脯氨酸代谢、碳水化合物代谢和脂肪酸代谢。随机森林弃一法交叉验证分析表明,肌酐是三组中最重要的代谢产物。与哺乳组仔猪比较,对照组仔猪血清肌酐浓度降低了754.58%(P=0.00001),Gln添加使其比对照组增加了447.39%(P=0.0003)。断奶仔猪与哺乳仔猪相关代谢网络反映早期断奶改变机体代谢途径,导致碳水化合物代谢、氨基酸代谢和脂质代谢异常,饲粮中添加Gln可在一定程度上改善仔猪的代谢过程。本试验为研究仔猪早期断奶与饲粮添加Gln对机体复杂的代谢变化提供了新的视角。
试验三：Gln对断奶仔猪总肠道表观消化率(CTTAD)、回肠末端表观消化率(AID)以及小肠中与营养吸收和能量代谢相关酶影响的研究至今未见报道,本试验主要探讨了Gln对断奶仔猪CTTAD、AID、小肠消化吸收相关因子和Gln及能量代谢酶活力的影响。仔猪21日龄断奶,分成两组,为Gln组和对照组,其日粮分别添加1%Gln(wt：wt)和等氮Ala。本研究包括两个独立的实验,分别为实验一和实验二,其中实验一：在断奶后3、5、10、15、30d测定日粮组分及能量的总肠道表观消化率；实验二：在10和30d比较两组仔猪的生长性能、AID、空肠酶活力、哺乳动物雷帕霉素靶蛋白(mTOR)和过氧化物酶体增殖体激活受体-γ(PPARy)和丙酮酸激酶(PK)基因表达差异。结果发现：日粮添加Gln显著提高干物质、有机物、总能和氨基酸的总肠道表观消化率(P<0.05),且总肠道表观消化率随着断奶后时间的延长显著提高(P<0.05)。在整个实验阶段,Gln组平均日增重增加了12.40%(P=0.049)。在断奶后10d,日粮Gln组总能、亮氨酸、赖氨酸、胱氨酸和脯氨酸回肠表观消化率分别提高了12.50%(P=0.047)、7.03%(P=0.041)、5.95%(P=0.036)、9.30%(P=0.025)和11.17%(P=0.009)；在断奶后30d,脯氨酸回肠表观消化率提高了6.11%(P=0.044)。空肠刷状缘碱性磷酸酶活力在断奶后10d和30d分别提高了30.36%(P=0.048)和6.21%(P=0.30)。与对照组比较,在断奶后10d(?)30d,Gln组PPARγmRNA含量分别下降了10.85%(P=0.14)和41.88%(P=0.023)；mTOR mRNA含量分别增加了22.10%(P=0.061)和22.28%(P=0.042)。Gln组谷氨酰胺合成酶活力在断奶后10d下降了48.89%(P=0.044),PK活力在断奶后30d下降了13.13%(P=0.036),谷丙转氨酶活力在断奶后30d表现为升高的趋势(P=0.076)。PK mRNA水平在断奶后10d和30d分别下降了29.75%(P=0.062)和44.40%(P=0.039)。结果提示,饲粮添加1%Gln提高日粮组分总肠道表观消化率和回肠末端表观消化率,改善小肠消化吸收能力,调节空肠中Gln代谢和能量代谢相关酶活力。
试验四：本试验旨在研究仔猪日粮中添加1%Gln对仔猪血清代谢谱的影响,以及对肝脏代谢的调节作用。16头健康的21日龄断奶仔猪随机分成两组：Gln组和对照组,其日粮分别添加1%Gln(wt:wt)和等氮Ala。处理30d后,采集血清样本研究其代谢物变化。另外,每组屠宰4头仔猪收集肝脏样本,分析其代谢调节酶活力和基因表达。结果显示：与对照组比较,Gln组仔猪血清有12种代谢物浓度发生了显著变化(P<0.05),包括碳水化合物、氨基酸、脂肪酸。这些数据结合KEGG代谢通路分析表明,对照组和Gln组仔猪在碳水化合物代谢、精氨酸和脯氨酸代谢、酪氨酸代谢和甘油磷酸酯代谢方面均有很大的差异。随机森林弃一法交叉分析验证分析表明,脯氨酸是12种显著性差异代谢物中对两组分开贡献率最大的代谢物。主成分分析显示,对照组和Gln组在得分图中各自分开聚集。Gln组仔猪肝脏丙氨酸转氨酶和已糖激酶的活力分别比对照组增加了26.77%(P=0.026)和26.18%(P=0.004),PK降低了29.08%(P=0.001)；PKmRNA水平降低66.10%(P=0.034)。mTOR和PPAR-γ mRNA水平在两组中无显著差异(P>0.05)。基于Gln组和对照组数据进行相关代谢网络分析,说明饲粮Gln处理改变了早期断奶仔猪的碳水化合物、脂类和氨基酸代谢。
试验五：本试验旨在分析Gln对氧化损伤诱导细胞凋亡的影响。采用0.35mMH2O2处理HT-29细胞,在无Gln的DMEM培养基中加入Gln,使Gln终浓度分别为0mM(对照组)、0.5mM、2mM和10mM。在12h后,SOD舌性和MDA含量在不同浓度Gln作用下无显著差异(P>0.05)。在24h后,对照组SOD活力显著低于0.5mM和2mM Gln组(P<0.05)。在32h后,0.5mM、2mM和10mMGln组SOD活力与对照组比较,分别升高了46.40%、67.99%和19.71%；MDA含量分别减少了17.79%、37.66%和13.09%。0.5mM和2mM Gln减少FAS、Caspase-3、NF-kB和Bax基因表达(P<0.05),增加Bcl-2基因表达(P<0.05)。在32h后,10mM Gln促进FAS、Caspase-3、NF-kB和Bax基因表达(P<0.05)。流式细胞仪检测发现,在24h后,Gln使活细胞数量提高了5.32%-11.97%；在32h后,活细胞数量提高了1.39%-7.63%。结果提示,Gln可提高细胞抗氧化能力和促进抑制细胞凋亡相关基因表达,降低细胞凋亡相关基因表达,从而阻止氧化损伤诱导的肠道细胞凋亡。
综上所述,早期断奶影响仔猪体内氨基酸、蛋白质、碳水化合物和脂质代谢。饲粮中添加1%谷氨酰胺抑制氧化应激诱导肠道上皮细胞的凋亡,提高饲料组分的消化率,调节肠道和肝脏等组织的代谢活动,从而对仔猪机体代谢有一定的改善作用。
The piglets are commonly weaned early to enhance the productive efficiency in modern pig farms. However, early weaning often causes stress in piglets, which exerts serious influence on the growth and metabolism. In the present study, time-related changes of amino acid (AA) profiles in weanling piglets were assessed based on metabonomic method, the effects of dietary L-glutamine (Gln) supplementation on nutrient digestibility and metabolism were estimated, and the mechanism regarding Gln inhibiting oxidant-induced apoptosis in enterocyte was also discussed. The main contents and results in the current study are as follows:
Trial1. The time-course of serum AA following response to early weaning was investigated over a30d period in weanling piglets using AA analyzer. Eight21-d old piglets were selected and their blood samples were collected on d0,1,3,5,7,10,15, and30post-weaning. Serum concentrations of arginine (Arg) and its immediate precursors (citrulline and ornithine) decreased (P<0.05) from d0to5post-weaning, and increased from d7to30post-weaning. Serum concentrations of leucine, proline (Pro), tyrosine (Tyr), and taurine decreased (P<0.05) on d1and3post-weaning, and increased to the level of d0post-weaning on d30. Serum concentrations of isoleucine, lysine (Lys), glycine, and serine were lowest on d5post-weaning; histidine, phenyalaine, valine, aspartate, and serine were lowest on d10post-weaning, which then increased thereafter. Methionine concentration changed slightly (P>0.05) from d0to3post-weaning, while it increased by43.51%(P<0.05) and41.11%(P<0.05) on d5compared with that on d1and3post-weaning, and kept constant thereafter. Serum concentration of threonine increased by31.67%(P<0.05) and79.06%(P<0.05) on d3post-weaning compared with that on d0and1, and then decreased on d15and30post-weaning. Serum concentration of Gln and dutamatc (Glu) were relatively higher (P<0.05) from d3to5, and d15to30than that on d0and1post-weaning. Total AA was relatively higher (P<0.05) on d0than those from d1to30post-weaning, and it decreased from d1to5, then increased on d7and keep constant thereafter. In score plot of principal component analysis, the profiles of AA were gradually away from the profile of AA on d0post-weaning, and then were closed to that, and tended to be stable. On d3and5postweaning, the profiles of AA were robustly altered. The pattern of partial least-square discriminant analysis demonstrated that Gln and Glu played the most important role in differentiating the profiles of AA at different time point post-weaning.
Trial2. A novel metabolomic method based on gas chromatography-mass spectrometry (GC-MS) was applied to determine the metabolites in the serum of piglets in response to weaning and dietary Gln supplementation. Thirty-six21-d-old piglets were randomly assigned into three groups. One group continued to suckle from the sows (suckling group), whereas the other two groups were weaned and their diets were supplemented with1%Gln (wt:wt) or isonitrogenous L-alanino (Ala), respectively, representing Gln group or control group. Serum samples were collected to characterize metabolites after a7-d treatment. Results showed twenty metabolites were down-regulated significantly (P<0.05) in control piglets compared with suckling ones. These data demonstrate that early weaning causes a wide range of metabolic changes across Arg and Pro metabolism, aminosugar and nucleotide metabolism, galactose metabolism, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acid, and fatty acid metabolism. Dietary Gln supplementation increased the levels of creatinine, D-xylose,2-hydroxybutyric acid, palmitelaidic acid, and a-L-galactofuranose (P<0.05) in early weaned piglets, and were involved in the arginine and proline metabolism, carbohydrate metabolism, and fatty acid metabolism. A leave-one-out cross-validation (LOOCV) of random forest analysis indicated that creatinine was the most important metabolite among the three groups. Notably, the concentration of creatinine in control piglets was decreased754.58%(P=0.00001) compared to the suckling piglets, and increased447.39%(P=0.0003) in Gln-supplemented piglets. A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways, leading to the abnormality of carbohydrate metabolism, AA metabolism and lipid metabolism, which could be partially improved by dietary Gln supplementation. These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.
Trial3. Gln has an essential role with a beneficial function in improving the nutrition status of young mammals. The influence of Gln on the coefficient of total tract apparent digestibility (CTTAD) and apparent ileal digestibility (AID), the jejunal enzyme activity associated with nutrient absorption, and the energy production in weaned piglets has not been sufficiently studied. The aim of the present paper is to provide a profile of the effects of Gln on CTTAD, AID, the activities of jejunal enzymes in connection with nutrient digestion and absorption and energy production. The piglets were weaned at21d of age. There were two groups in Exp.1and Exp.2, representing supplementation with0or1%Gln to the basal diet. In Exp.1, the CTTAD of the dietary components and energy was assessed at3,5,10,15, and30d after weaning. In Exp.2, productive performance, AID, jejunal enzyme activities, and expression of peroxisome proliferator-activated receptor gamma (PPARy), mammalian target of rapamycin (mTOR), and pyruvate kinase (PK) were measured at10and30d post-weaning. Results showed that dietary Gln supplementation significantly improved (P<0.05) the CTTAD of DM, OM, GE, and AA, and the CTTAD increased significantly (P<0.05) with the increasing days after weaning. For the entire experiment, the average daily gain increased by12.40%(P=0.049) in the Gln group. Dietary Gln supplementation increased the AID of GE, Leu, Lys, Cys, and Pro by12.50%(P=0.047),7.03%(P=0.041),5.95%(P=0.036),9.30%(P=0.025),11.17%(P=0.009), respectively, at10d post-weaning; Pro by6.11%(P=0.044) at30d post-weaning. Jejunal brush border membrane-bound alkaline phosphatase activity increased in the Gln-supplemented pigs by30.36%(P=0.048) and6.21%(P=0.30) at10and30d post-weaning, respectively. Compared with the control pigs, the mRNA level of PPARy decreased by10.85%(P=0.14) and41.88%(P=0.023) after the administration of1%Gln for10and30d, respectively. The mRNA level of mTOR increased by22.10%(P=0.061) and22.28%(P=0.042), respectively. The activity of Gln synthetase decreased by48.89%(P=0.044) at10d post-weaning, and pyruvate kinase (PK) by13.13%(P=0.036) at30d post-weaning in the Gln-supplemented pigs. The Ala aminotransferase activity was numerically elevated (P=0.076) in the Gln group. The mRNA level of PK decreased by29.75%(P0.062) and44.40%(P=0.039) for the Gln supplementation for10and30d, respectively. In conclusion,1%Gln supplementation to the post-weaned piglet diet enhanced the CTTAD and AID of diet, improved intestinal absorption, and modified jejunal enzyme activities related to Gln metabolism and energy production.
Trial4. A novel metabolomic method based on GC-MS was applied to investigate serum metabolites in response to dietary Gln supplementation in piglets. Sixteen21-d-old pigs were weaned and randomly assigned into treatments, which were1) Gkn supplementation and2) control, representing1%Gln (wt:wt) and isonitrogenous Ala, respectively. Serum samples were collected to characterize metabolites after a30-d treatment. Additionally,4liver samples per treatment were collected to examine enzyme activity and gene expression involved in metabolic regulation. Results indicated that12metabolites were altered (P<0.05) by Gln treatment, including carbohydrates, AA, and fatty acids. A LOOCV of random forest analysis indicated that Pro was the most important metabolites among the12different metabolites. These data demonstrate that the control and Gln-supplemented pigs differed (P<0.05) in terms of metabolism of carbohydrates, Pro.Tvr. and glycerophospholipids. Principal component analysis yielded separate clustering of profiles between the Gin and control groups. Metabolic enzyme activities of Ala aminotransferase and hexokinase increased by26.77%(P=0.026) and26.18%(P=0.004) in liver of Gln-supplemented pigs over the control, respectively, whereas PK activity decreased by29.08%(P=0.001). The gene expression of PK in liver deereased by66.10%(P=0.034) by Gln treatment for30d. No differences were observed for the mRNA levels of mTOR and PPARy. Based on the data, correlation network for the Gln-supplemented pigs and the control pigs indicated that Gin treatment affected carbohydrate, lipid and△A metabolism in the whole body of the early weaned piglets. These findings provide fresh insight into specific metabolic pathways and lay the groundwork for the complex metabolic alteration in response to dietary Gln supplementation in pigs.
Trial5. This experiment tested the hypothesis that Gln prevents oxidant-induced death of enterocytes. HT-29cells were cultured for12h,24h, and32h, respectively, in Gln-free Dulbecco's modified Eagle's-F12Ham medium containing0,0.5,2.0or10.0mM Gln, and0.35mM H2O2. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) formation were slightly changed (P>0.05) after administration of Gln for12h, while SOD activity increased and MDA formation decreased (P<0.05) for24h and32h. Administration of0.5and2.0mM Gln decreased mRNA level of FAS, Caspase-3, NF-kB, and Bax (P<0.05), and increased Bcl-2mRNA level, whereas administration of10.0mM Gln increased mRNA level of FAS, Caspase-3, NF-kB, and Bax (P<0.05) at32h after incubation. The live cells increased by5.32%～11.97%at24h after administration of Gln, and by1.39%～7.63%at32h. Therefore, these results suggest that Gln can promote antioxidant capacity and anti-apoptosis gene expression in enterocytes, and reduce pro-apoptosis gene expression to inhibit oxidant-induced apoptosis.
In conclusion, early weaning influences AA, protein, carbohydrate, and lipid metabolism in piglets. Dietary1%Gln supplementation inhibits oxidant-induced apoptosis of enterocytes, increases nutrient digestibility, regulate the metabolic activities of intestine and liver, which results in the improvement of body metabolism in young pigs.
试验一：本试验的主要目的是分析仔猪早期断奶过程中血清氨基酸代谢谱的动态变化。选取8头21日龄断奶仔猪,在断奶后0、1、3、5、7、10、15、30d采集血液样本用于氨基酸分析。试验结果显示,血清精氨酸与其直接的前体物质瓜氨酸和鸟氨酸含量在断奶后1～5d内显著下降(P<0.05),在断奶后7-30d上升。亮氨酸、脯氨酸、酪氨酸和牛磺酸在断奶后1～3d内显著下降(P<0.05),然后其含量上升。异亮氨酸、赖氨酸、甘氨酸和丝氨酸含量在断奶后5d显著低于其他时间点的含量,然后在断奶后7-30d上升。蛋氨酸含量在断奶后0-3d内变化较小(P>0.05),在断奶后5d,其含量分别比断奶后0d、1d和3d增加了41.61%(P<0.05)、43.51%(P<0.05)和41.11%(P<0.05),之后保持稳定。血清苏氨酸含量在断奶后3d比断奶后O d和1d分别增加了31.67%(P<0.05)和79.06%(P<0.05),断奶后10d其达到最大值,在断奶后15d和30d其含量显著降低。谷氨酸含量(包括谷氨酸+谷氨酰胺)在断奶后0d、1d和10d显著低于其他时间段含量(P<0.05)。总氨基酸含量在断奶后0d显著高于断奶后各时间段总氨基酸含量(P<0.05),在断奶后1-5d,总氨基酸含量逐渐降低,断奶后7d起升高并至断奶后30d无显著变化(P>0.05)。主成分分析得分图显示,随着断奶后时间的延长,血清氨基酸代谢谱与断奶后O d的代谢谱差异逐渐变大,然后逐渐向断奶后0d代谢谱位置靠拢,并趋于稳定,其中断后3-5d血清氨基酸代谢谱变化幅度最大。偏最小二乘法判别分析模型显示,谷氨酰胺和谷氨酸为在NRC(1998)饲养标准下区分断奶后各时间点血清代谢谱最重要的氨基酸。
试验二：基于气相色谱/质谱联用技术的代谢组学方法运用于研究仔猪早期断奶与饲粮中补充L-谷氨酰胺(Gln)对血清代谢物的影响。将36头21日龄仔猪随机分成三组,一组继续哺乳(哺乳组),另外两组仔猪进行断奶处理,分别在其日粮中添加1%Gln或等氮的L-丙氨酸(Ala),即为Gln组与对照组。处理7d后采集血清样本进行研究。结果显示,与哺乳组相比,对照组仔猪中有20种代谢物含量显著下降(P<0.05)。这些数据结合KEGG数据库代谢通路分析表明,早期断奶引起广泛的代谢改变,包括精氨酸和脯氨酸代谢、氨基糖和核苷酸代谢、乳糖代谢、甘油磷酸酯代谢、不饱和脂肪酸的生物合成和脂肪酸代谢。饲粮添加Gln能提高仔猪血清肌酐、D-木糖、2-羟丁酸、反式-9-十六烯酸、α-L-呋喃半乳糖含量(P<0.05)。这些物质涉及精氨酸和脯氨酸代谢、碳水化合物代谢和脂肪酸代谢。随机森林弃一法交叉验证分析表明,肌酐是三组中最重要的代谢产物。与哺乳组仔猪比较,对照组仔猪血清肌酐浓度降低了754.58%(P=0.00001),Gln添加使其比对照组增加了447.39%(P=0.0003)。断奶仔猪与哺乳仔猪相关代谢网络反映早期断奶改变机体代谢途径,导致碳水化合物代谢、氨基酸代谢和脂质代谢异常,饲粮中添加Gln可在一定程度上改善仔猪的代谢过程。本试验为研究仔猪早期断奶与饲粮添加Gln对机体复杂的代谢变化提供了新的视角。
试验三：Gln对断奶仔猪总肠道表观消化率(CTTAD)、回肠末端表观消化率(AID)以及小肠中与营养吸收和能量代谢相关酶影响的研究至今未见报道,本试验主要探讨了Gln对断奶仔猪CTTAD、AID、小肠消化吸收相关因子和Gln及能量代谢酶活力的影响。仔猪21日龄断奶,分成两组,为Gln组和对照组,其日粮分别添加1%Gln(wt：wt)和等氮Ala。本研究包括两个独立的实验,分别为实验一和实验二,其中实验一：在断奶后3、5、10、15、30d测定日粮组分及能量的总肠道表观消化率；实验二：在10和30d比较两组仔猪的生长性能、AID、空肠酶活力、哺乳动物雷帕霉素靶蛋白(mTOR)和过氧化物酶体增殖体激活受体-γ(PPARy)和丙酮酸激酶(PK)基因表达差异。结果发现：日粮添加Gln显著提高干物质、有机物、总能和氨基酸的总肠道表观消化率(P<0.05),且总肠道表观消化率随着断奶后时间的延长显著提高(P<0.05)。在整个实验阶段,Gln组平均日增重增加了12.40%(P=0.049)。在断奶后10d,日粮Gln组总能、亮氨酸、赖氨酸、胱氨酸和脯氨酸回肠表观消化率分别提高了12.50%(P=0.047)、7.03%(P=0.041)、5.95%(P=0.036)、9.30%(P=0.025)和11.17%(P=0.009)；在断奶后30d,脯氨酸回肠表观消化率提高了6.11%(P=0.044)。空肠刷状缘碱性磷酸酶活力在断奶后10d和30d分别提高了30.36%(P=0.048)和6.21%(P=0.30)。与对照组比较,在断奶后10d(?)30d,Gln组PPARγmRNA含量分别下降了10.85%(P=0.14)和41.88%(P=0.023)；mTOR mRNA含量分别增加了22.10%(P=0.061)和22.28%(P=0.042)。Gln组谷氨酰胺合成酶活力在断奶后10d下降了48.89%(P=0.044),PK活力在断奶后30d下降了13.13%(P=0.036),谷丙转氨酶活力在断奶后30d表现为升高的趋势(P=0.076)。PK mRNA水平在断奶后10d和30d分别下降了29.75%(P=0.062)和44.40%(P=0.039)。结果提示,饲粮添加1%Gln提高日粮组分总肠道表观消化率和回肠末端表观消化率,改善小肠消化吸收能力,调节空肠中Gln代谢和能量代谢相关酶活力。
试验四：本试验旨在研究仔猪日粮中添加1%Gln对仔猪血清代谢谱的影响,以及对肝脏代谢的调节作用。16头健康的21日龄断奶仔猪随机分成两组：Gln组和对照组,其日粮分别添加1%Gln(wt:wt)和等氮Ala。处理30d后,采集血清样本研究其代谢物变化。另外,每组屠宰4头仔猪收集肝脏样本,分析其代谢调节酶活力和基因表达。结果显示：与对照组比较,Gln组仔猪血清有12种代谢物浓度发生了显著变化(P<0.05),包括碳水化合物、氨基酸、脂肪酸。这些数据结合KEGG代谢通路分析表明,对照组和Gln组仔猪在碳水化合物代谢、精氨酸和脯氨酸代谢、酪氨酸代谢和甘油磷酸酯代谢方面均有很大的差异。随机森林弃一法交叉分析验证分析表明,脯氨酸是12种显著性差异代谢物中对两组分开贡献率最大的代谢物。主成分分析显示,对照组和Gln组在得分图中各自分开聚集。Gln组仔猪肝脏丙氨酸转氨酶和已糖激酶的活力分别比对照组增加了26.77%(P=0.026)和26.18%(P=0.004),PK降低了29.08%(P=0.001)；PKmRNA水平降低66.10%(P=0.034)。mTOR和PPAR-γ mRNA水平在两组中无显著差异(P>0.05)。基于Gln组和对照组数据进行相关代谢网络分析,说明饲粮Gln处理改变了早期断奶仔猪的碳水化合物、脂类和氨基酸代谢。
试验五：本试验旨在分析Gln对氧化损伤诱导细胞凋亡的影响。采用0.35mMH2O2处理HT-29细胞,在无Gln的DMEM培养基中加入Gln,使Gln终浓度分别为0mM(对照组)、0.5mM、2mM和10mM。在12h后,SOD舌性和MDA含量在不同浓度Gln作用下无显著差异(P>0.05)。在24h后,对照组SOD活力显著低于0.5mM和2mM Gln组(P<0.05)。在32h后,0.5mM、2mM和10mMGln组SOD活力与对照组比较,分别升高了46.40%、67.99%和19.71%；MDA含量分别减少了17.79%、37.66%和13.09%。0.5mM和2mM Gln减少FAS、Caspase-3、NF-kB和Bax基因表达(P<0.05),增加Bcl-2基因表达(P<0.05)。在32h后,10mM Gln促进FAS、Caspase-3、NF-kB和Bax基因表达(P<0.05)。流式细胞仪检测发现,在24h后,Gln使活细胞数量提高了5.32%-11.97%；在32h后,活细胞数量提高了1.39%-7.63%。结果提示,Gln可提高细胞抗氧化能力和促进抑制细胞凋亡相关基因表达,降低细胞凋亡相关基因表达,从而阻止氧化损伤诱导的肠道细胞凋亡。
综上所述,早期断奶影响仔猪体内氨基酸、蛋白质、碳水化合物和脂质代谢。饲粮中添加1%谷氨酰胺抑制氧化应激诱导肠道上皮细胞的凋亡,提高饲料组分的消化率,调节肠道和肝脏等组织的代谢活动,从而对仔猪机体代谢有一定的改善作用。
The piglets are commonly weaned early to enhance the productive efficiency in modern pig farms. However, early weaning often causes stress in piglets, which exerts serious influence on the growth and metabolism. In the present study, time-related changes of amino acid (AA) profiles in weanling piglets were assessed based on metabonomic method, the effects of dietary L-glutamine (Gln) supplementation on nutrient digestibility and metabolism were estimated, and the mechanism regarding Gln inhibiting oxidant-induced apoptosis in enterocyte was also discussed. The main contents and results in the current study are as follows:
Trial1. The time-course of serum AA following response to early weaning was investigated over a30d period in weanling piglets using AA analyzer. Eight21-d old piglets were selected and their blood samples were collected on d0,1,3,5,7,10,15, and30post-weaning. Serum concentrations of arginine (Arg) and its immediate precursors (citrulline and ornithine) decreased (P<0.05) from d0to5post-weaning, and increased from d7to30post-weaning. Serum concentrations of leucine, proline (Pro), tyrosine (Tyr), and taurine decreased (P<0.05) on d1and3post-weaning, and increased to the level of d0post-weaning on d30. Serum concentrations of isoleucine, lysine (Lys), glycine, and serine were lowest on d5post-weaning; histidine, phenyalaine, valine, aspartate, and serine were lowest on d10post-weaning, which then increased thereafter. Methionine concentration changed slightly (P>0.05) from d0to3post-weaning, while it increased by43.51%(P<0.05) and41.11%(P<0.05) on d5compared with that on d1and3post-weaning, and kept constant thereafter. Serum concentration of threonine increased by31.67%(P<0.05) and79.06%(P<0.05) on d3post-weaning compared with that on d0and1, and then decreased on d15and30post-weaning. Serum concentration of Gln and dutamatc (Glu) were relatively higher (P<0.05) from d3to5, and d15to30than that on d0and1post-weaning. Total AA was relatively higher (P<0.05) on d0than those from d1to30post-weaning, and it decreased from d1to5, then increased on d7and keep constant thereafter. In score plot of principal component analysis, the profiles of AA were gradually away from the profile of AA on d0post-weaning, and then were closed to that, and tended to be stable. On d3and5postweaning, the profiles of AA were robustly altered. The pattern of partial least-square discriminant analysis demonstrated that Gln and Glu played the most important role in differentiating the profiles of AA at different time point post-weaning.
Trial2. A novel metabolomic method based on gas chromatography-mass spectrometry (GC-MS) was applied to determine the metabolites in the serum of piglets in response to weaning and dietary Gln supplementation. Thirty-six21-d-old piglets were randomly assigned into three groups. One group continued to suckle from the sows (suckling group), whereas the other two groups were weaned and their diets were supplemented with1%Gln (wt:wt) or isonitrogenous L-alanino (Ala), respectively, representing Gln group or control group. Serum samples were collected to characterize metabolites after a7-d treatment. Results showed twenty metabolites were down-regulated significantly (P<0.05) in control piglets compared with suckling ones. These data demonstrate that early weaning causes a wide range of metabolic changes across Arg and Pro metabolism, aminosugar and nucleotide metabolism, galactose metabolism, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acid, and fatty acid metabolism. Dietary Gln supplementation increased the levels of creatinine, D-xylose,2-hydroxybutyric acid, palmitelaidic acid, and a-L-galactofuranose (P<0.05) in early weaned piglets, and were involved in the arginine and proline metabolism, carbohydrate metabolism, and fatty acid metabolism. A leave-one-out cross-validation (LOOCV) of random forest analysis indicated that creatinine was the most important metabolite among the three groups. Notably, the concentration of creatinine in control piglets was decreased754.58%(P=0.00001) compared to the suckling piglets, and increased447.39%(P=0.0003) in Gln-supplemented piglets. A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways, leading to the abnormality of carbohydrate metabolism, AA metabolism and lipid metabolism, which could be partially improved by dietary Gln supplementation. These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.
Trial3. Gln has an essential role with a beneficial function in improving the nutrition status of young mammals. The influence of Gln on the coefficient of total tract apparent digestibility (CTTAD) and apparent ileal digestibility (AID), the jejunal enzyme activity associated with nutrient absorption, and the energy production in weaned piglets has not been sufficiently studied. The aim of the present paper is to provide a profile of the effects of Gln on CTTAD, AID, the activities of jejunal enzymes in connection with nutrient digestion and absorption and energy production. The piglets were weaned at21d of age. There were two groups in Exp.1and Exp.2, representing supplementation with0or1%Gln to the basal diet. In Exp.1, the CTTAD of the dietary components and energy was assessed at3,5,10,15, and30d after weaning. In Exp.2, productive performance, AID, jejunal enzyme activities, and expression of peroxisome proliferator-activated receptor gamma (PPARy), mammalian target of rapamycin (mTOR), and pyruvate kinase (PK) were measured at10and30d post-weaning. Results showed that dietary Gln supplementation significantly improved (P<0.05) the CTTAD of DM, OM, GE, and AA, and the CTTAD increased significantly (P<0.05) with the increasing days after weaning. For the entire experiment, the average daily gain increased by12.40%(P=0.049) in the Gln group. Dietary Gln supplementation increased the AID of GE, Leu, Lys, Cys, and Pro by12.50%(P=0.047),7.03%(P=0.041),5.95%(P=0.036),9.30%(P=0.025),11.17%(P=0.009), respectively, at10d post-weaning; Pro by6.11%(P=0.044) at30d post-weaning. Jejunal brush border membrane-bound alkaline phosphatase activity increased in the Gln-supplemented pigs by30.36%(P=0.048) and6.21%(P=0.30) at10and30d post-weaning, respectively. Compared with the control pigs, the mRNA level of PPARy decreased by10.85%(P=0.14) and41.88%(P=0.023) after the administration of1%Gln for10and30d, respectively. The mRNA level of mTOR increased by22.10%(P=0.061) and22.28%(P=0.042), respectively. The activity of Gln synthetase decreased by48.89%(P=0.044) at10d post-weaning, and pyruvate kinase (PK) by13.13%(P=0.036) at30d post-weaning in the Gln-supplemented pigs. The Ala aminotransferase activity was numerically elevated (P=0.076) in the Gln group. The mRNA level of PK decreased by29.75%(P0.062) and44.40%(P=0.039) for the Gln supplementation for10and30d, respectively. In conclusion,1%Gln supplementation to the post-weaned piglet diet enhanced the CTTAD and AID of diet, improved intestinal absorption, and modified jejunal enzyme activities related to Gln metabolism and energy production.
Trial4. A novel metabolomic method based on GC-MS was applied to investigate serum metabolites in response to dietary Gln supplementation in piglets. Sixteen21-d-old pigs were weaned and randomly assigned into treatments, which were1) Gkn supplementation and2) control, representing1%Gln (wt:wt) and isonitrogenous Ala, respectively. Serum samples were collected to characterize metabolites after a30-d treatment. Additionally,4liver samples per treatment were collected to examine enzyme activity and gene expression involved in metabolic regulation. Results indicated that12metabolites were altered (P<0.05) by Gln treatment, including carbohydrates, AA, and fatty acids. A LOOCV of random forest analysis indicated that Pro was the most important metabolites among the12different metabolites. These data demonstrate that the control and Gln-supplemented pigs differed (P<0.05) in terms of metabolism of carbohydrates, Pro.Tvr. and glycerophospholipids. Principal component analysis yielded separate clustering of profiles between the Gin and control groups. Metabolic enzyme activities of Ala aminotransferase and hexokinase increased by26.77%(P=0.026) and26.18%(P=0.004) in liver of Gln-supplemented pigs over the control, respectively, whereas PK activity decreased by29.08%(P=0.001). The gene expression of PK in liver deereased by66.10%(P=0.034) by Gln treatment for30d. No differences were observed for the mRNA levels of mTOR and PPARy. Based on the data, correlation network for the Gln-supplemented pigs and the control pigs indicated that Gin treatment affected carbohydrate, lipid and△A metabolism in the whole body of the early weaned piglets. These findings provide fresh insight into specific metabolic pathways and lay the groundwork for the complex metabolic alteration in response to dietary Gln supplementation in pigs.
Trial5. This experiment tested the hypothesis that Gln prevents oxidant-induced death of enterocytes. HT-29cells were cultured for12h,24h, and32h, respectively, in Gln-free Dulbecco's modified Eagle's-F12Ham medium containing0,0.5,2.0or10.0mM Gln, and0.35mM H2O2. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) formation were slightly changed (P>0.05) after administration of Gln for12h, while SOD activity increased and MDA formation decreased (P<0.05) for24h and32h. Administration of0.5and2.0mM Gln decreased mRNA level of FAS, Caspase-3, NF-kB, and Bax (P<0.05), and increased Bcl-2mRNA level, whereas administration of10.0mM Gln increased mRNA level of FAS, Caspase-3, NF-kB, and Bax (P<0.05) at32h after incubation. The live cells increased by5.32%～11.97%at24h after administration of Gln, and by1.39%～7.63%at32h. Therefore, these results suggest that Gln can promote antioxidant capacity and anti-apoptosis gene expression in enterocytes, and reduce pro-apoptosis gene expression to inhibit oxidant-induced apoptosis.
In conclusion, early weaning influences AA, protein, carbohydrate, and lipid metabolism in piglets. Dietary1%Gln supplementation inhibits oxidant-induced apoptosis of enterocytes, increases nutrient digestibility, regulate the metabolic activities of intestine and liver, which results in the improvement of body metabolism in young pigs.
引文
Adahchour, M., Bmndt, M., Baier, H.U., Vreuls, R.J.J., Batenburg, A.M., Brinkman, U.A.T. Comprehensive two-dimensional gas chromatography coupled to a rapid-scanning quadrupole mass spectrometer:principles and applications. Journal of Chromatography A,2005,1067:245-254.
Antonov, A.V., Dietmann, S., Mewes, H.W. KEGG spider:interpretation of genomics data in the context of the global gene metabolic network. Genome Biology,2008, 9:R179.
AOAC,2000. Official Methods of Analysis.17th edn. Association of Official Analytical Chemists, Arlington, Virginia.
Ardawi, M.S.M. Glutamine and glucose metabolism in human peripheral lymphocytesl. Metabolism,1988,37:99-103.
Barszcz, M. Skomial, J. The development of the small intestine of piglets-chosen aspects. Journal of Animal and Feed Sciences,2011,20:3-15.
Bazinet, R.P., McMillan, E.G., Seebaransingh, R., Hayes, A.M., Cunnane, S.C. Whole-body β-oxidation of 18:2ω6 and 18:3co3 in the pig varies marked ly with weaning strategy and dietary 18:3co3. Journal of Lipid Research,2003,44: 314-319.
Bertolo, R.F.P., Brunton, J.A., Pencharz, P.B., Ball, R.O. Arginine, ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs. American Journal of Physiology Endocrinology Metabolism,2003,284: 915-922.
Bertram, H.C., Hoppe, C., Petersen, B.O., Duus, J.O., Molgaard, C., Michaelsen, K.F. An NMR-based metabonomic investigation on effects of milk and meat protein diets given to 8-year-old boys. British Journal of Nutrition,2007,97:758-763.
Biener, G.P., Schjoerring, J.K., Jahn, T.P. Membrane transport of hydrogen peroxide. Biochimica et Biophysica Acta (BBA)-Biomembranes,2006,1758:994-1003.
Blachier, F., Claire, B., Bos, C., Tome, D. Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines.The American Journal of Clinical Nutrition,2009,90:814-821.
Board, M., Humm, S., Newsholme, E.A. Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochemical Journal,1990,262: 503-509.
Boza, J.J., Moennoz, D., Bournot, C.E., Blum, S., Zbinden, I., Finot, P.A., Ballevre, O. Role of glutamine on the de novo purine nucleotide synthesis in Caco-2 cells. European Journal of Nutrition,2000,39:38-46.
Breiman, L. Random Forests. Machine Learning,2001,45:5-32.
Brosnan, J.T., Wijekoon, E.P., Warford-Woolgar, L., Trottier, N.L., Brosnan, M.E., Brunton, J.A., Bertolo, R.F.P. Creatine synthesis is a major metabolic process in neonatal niglets and has important implications for amino acid metabolism and methyl balance. The Journal of Nutrition,2009,139:1292-1297.
Bruininx, E.M., Van der Peet-Schwering, C.M., Schrama, J.W., Vereijken, P.F., Vesseur, P.C., Everts, H., den Hartog, L.A., Beynen, A.C. Individually measured feed intake characteristics and growth performance of group-housed weanling pigs:effects of sex, initial body weight, and body weight distribution within groups. Journal of Animal Science,2001,79:301-308.
Cera, K.R., Mahan, D.C., Cross, R.F., Reinhart, G.A., Whitmoyer, R.E. Effect of age. weaning and postweaning diet on small intestinal growth and jejunal morphology in young swine. Journal of Animal Science,1988,66:574-584.
Cera, K.R., Mahan, D.C., Reinhart, G.A. Effect of weaning, week post-weaning and diet composition on pancreatic and small intestinal luminal lipase response in young swine. Journal of Animal Science,1990,68:384-391.
Chamorro, S., de Blas, C., Grant, G., Badiola, I., Menoyo, D., Carabano, R. Effect of dietary supplementation with glutamine and a combination of glutamine-arginine on intestinal health in 25-d-old weaned rabbits. Journal of Animal Science,2010, 88:170-180.
Chawla, A., Repa, J.J., Evans, R.M., Mangelsdorf, D.J. Nuclear receptors and lipid physiology:opening the X-files. Science,2001,294:1866-1870.
Chandra, J., Samali, A., Orrenius, S. Triggering and modulation of apoptosis by oxidative stress. Free Radical Biology and Medicine,2000,29:323-333.
Clowes, E.J., Aherne, F.X., Baracos, V.E. Skeletal muscle protein mobilization during the progression of lactation. American Journal of Physiology Endocrinology Metabolism,2004,288:E564-E572.
Coeffier, M., Claeyssens, S., Hecketsweiler, B., Lavoinne, A., Ducrotte, P., Dechelotte, P. Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa. American Journal of Physiology Gastrointestinal and Liver Physiology,2003,285:266-273.
Coss-Bu, J.A., Sunehag, A.L., Haymond, M.W. Contribution of galactose and fructose to glucose homeostasis. Metabolism,2009,58:1050-1058.
Curi, R., Lagranha, C.J., Doi, S.Q., Sellitti, D.F., Procopio, J., Pithon-Curi, T.C. Corless, M., Newsholme, P. Molecular mechanisms of glutamine action. Journal of Cellular Physiology,2005,204:392-401.
Darcy-Vrillon, B., Posho, L., Morell, M.T., Bernard, F., Blachier, F. Glucose, galactose, and glutamine metabolism in pig isolated enterocytes during development. Pediatric Research,1994,36:175-181.
Daykin, C.A., van Duynhoven, J.P.M., Groenewegen, A., Dachtler, M., Van Amelsvoort, J.M.M., Mulder, T.P.J. Nuclear magnetic resonance spectroscopic based studies of the metabolism of black tea polyphenols in humans. Journal of Agricultural and Food Chemistry,2005,53:1428-1434.
Deminice, R., Portari, G.V.,Vannucchi, H.,Jordao, A.A. Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats. British Journal of Nutrition,2009,102:110-116.
Denno, R., Rounds, J.D., Faris, R., Holejko, L.B., Wilmore, D.W. Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. Journal of Surgical Research,1996,61:35-38.
Dividich, J. L., Seve, B. Effects of underfeeding during the weaning period on growth, metabolism, and hormonal adjustments in the piglet. Domestic Animal Endocrinology,2000,19:63-74.
Evans, M.E., Jones, D.P., Ziegler, T.R. Glutamine Prevents Cytokine-Induced Apoptosis in Human Colonic Epithelial Cells. The Journal of Nutrition,2003, 133:3065-3071.
Fan, M.Z., Adeola, O., Asem, E.K., King, D. Postnatal ontogeny of kinetics of porcine jejunal brush border membrane-bound alkaline phosphatase, aminopeptidase N and sucrase activities. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology,2002,132:599-607.
Feng, B., Shiber, S.K. Max, S.R. Glutamine regulates glutamine synthetase expression in skeletal muscle cells in culture. Journal of Cellular Physiology,1990,145: 376-380.
Fiatte, C., Huin, C., Collet, P., Plenat, F., Dauca, M.,Schohn, H. Expression of PPARy is reduced by medium supplementation with L-glutamine in human colorectal Caco-2 cells. International Journal of Molecular Medicine,2008.22:825-832.
Fleming, S. E., Zambell, K. L., Fitch, M. D. Glucose and glutamine provide similar proportions of energy to mucosal cells of rat small intestine. American Journal of Physiology,1997,273:968-978.
Flynn. N.E., Knabe, D.A., Mallick, B.K., Wu, G. Postnatal changes of plasma amino acids in suckling pigs. Journal of Animal Science,2000,78:2369-2375.
Fujita, T., Yanaga, K. Association between glutamine extraction and release of citrulline and glycine by the human small intestine. Life Sciences,2007,80: 1846-1850.
Galli, A., Price, D., Crabb, D. High-level expression of rat class I alcohol dehydrogenase is sufficient for ethanol-induced fat accumulation in tranduced hela cells. Hepatology,1999,29:1164-1170.
Geddes, K., Philpott, D.J. A new role for intestinal alkaline phosphatase in gut barrier maintenance. Gastroenterology,2008,135:8-12.
Gong, J., Yu, H., Liu, T., Li, M., Si, W., de Lange, C.F.M., Dewey. C. Characterization of ileal bacterial microbiota in newly-weaned pigs in response to feeding lincomycin, organic acids or herbal extract. Livestock Science,2008,116: 318-322.
Grant, J. Use of L-glutamine in total parenteral nutrition. Journal of Surgical Research, 1998,44:506-513.
Guay, F., Trottier, N.L. Muscle growth and plasma concentrations of amino acids, insulin-like growth factor-I, and insulin in growing pigs fed reduced-protein diets. Journal of Animal Science,2006,84:3010-3019.
Gu, X., Li, D. Fat nutrition and metabolism in piglets:a review. Animal Feed Science and Technology,2003,109:151-170.
Gu, X., Li, D., She, R. Effect of weaning on small intestinal structure and function in the piglet. Archives of Animal Nutrition,2002,56:275-286.
Hammon, H., Blum, J.W. Prolonged colostrum feeding enhances xylose absorption in neonatal calves. Journal of Animal Science,1997,75:2915-2919.
Hampson, D.J., Kidder, D.E. Influence of creep feeding and weaning on brush borsh border enzyme activities in the piglet small intestine. Research in Veterinary Science,1986.40:24-31.
Hampson, D.J. Alteration in piglet small intestinal structure at weaning. Research in Veterinary Science,1986,40:32-40.
Haynes,T.E., Li, P., Li, X., Shimotori, K., Sato, H., Flynn, N.E., Wang, J., Knabe, D.A., Wu, G. L-Glutamine or L-alanyl-L-glutamine prevents oxidant-or endotoxin-induced death of neonatal enterocytes. Amino Acids,2009,37: 131-142.
He, Q., Ren, P., Kong, X., Wu, Y., Wu, G., Li, P., Hao, F., Tang, H., Blachier, F., Yin, Y. Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach. Journal of Nutritional Biochemistry,2012,23:133-139.
He. Q.H., Kong, X.F., Wu, G.Y., Ren, P.P., Tang, H.R., Hao, F.H., Huang, R.L., Li,T.J., Tan, B., Tang, Z.R., Yin, Y.L., Wu, Y.N. Metabolomic analysis of the response of growing pigs to dietary L-arginine supplementation. Amino Acids,2009,37: 199-208.
He, Q.H., Yin, Y.L., Zhao, F., Kong, X.F., Wu, G.Y., Ren, P.P. Metabonomics and its role in amino acid nutrition research. Frontiers in Bioscience,2011,16: 2451-2460.
Henning, S.J. Postnatal development:coordination of feeding, digestion, and metabolism. American Journal of Physiology Gastrointestinal and Liver Physiology,1981,24:199-214.
Hodin, R.A., Chamberlain, S.M., Meng, S. Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state. American Journal of Physiology Cell Physiology,1995,269:385-391.
Hubert-Buron, A., Leblond, J., Jacquot, A., Ducrotte, P., Dechelotte, P., Coiffier, M. Glutamine Pretreatment Reduces IL-8 Production in Human Intestinal Epithelial Cells by Limiting IκBα Ubiquitination. The Journal of Nutrition,2006,136: 1461-1465.
Hwang, J.J., Perera, S., Shapiro, R.A. Curthoys, Norman.P. Mechanism of altered renal glutaminase gene expression in response to chronic acidosis. Biochemistry, 1991,30:7522-7526.
Janczyk, P., Pieper, R., Smidt, H., Souffrant, W.B. Changes in the diversity of pig ileal lactobacilli around weaning determined by means of 16S rRNA gene amplification and denaturing gradient gel electrophoresis. FEMS Microbiology Ecology,2007,61:132-140.
Jia, Y., Lin, J., Mi, Y., Zhang, C. Quercetin attenuates cadmium-induced oxidative damage and apoptosis in granulosa cells from chicken ovarian follicles. Reproductive Toxicology,2011,31:477-485.
Jobgen, W.S., Fried, S.K., Fu, W.J., Meininger, C.J., Wu, G. Regulatory role for the arginine-nitric oxide pathway in energy-substrate metabolism. The Journal of Nutritional Biochemistry,2006,17:571-588.
Jones, D.P. Radical-free biology of oxidative stress. American Journal of Physiology Cell Physiology,2008,295:C849-C868.
Kim, S.W., Wu, G. Dietary arginine supplementation enhances the growth of milk-fed young pigs. The Journal of Nutrition,2004,134:625-630.
Kimball, S.R., Jefferson, L.S., Nguyen, H.V., Suryawan, A., Bush, J.A., Davis, T.A. Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process. American Journal of Physiology Endocrinology and Metabolism,2000,279:1080-1087.
Kirchgessner, M., Fickler, J., Roth, F.X. Effect of dietary proline supply on N-balance of piglets.3. Communication on the importance of nonessential amino acids for protein retention. Journal of Animal Physiology and Animal Nutrition,1995,73: 57-65.
Kong, X.F., Yin, Y.L., He, Q.H., Yin, F.G., Liu, H.J., Li, T.J., Huang, R.L., Geng, M.M., Ruan, Z., Deng, Z.Y., Xie, M.Y., Wu, G. Dietary supplementation with Chinese herbal powder enhances ileal digestibilities and serum concentrations of amino acids in young pigs. Amino Acids,2009,37:573-582.
Kozar, R.A., Schultz, S.G., Bick, R.J., Poindexter, B.J., DeSoignie, R., Moore, F.A. Enteral glutamine but not alanine maintains small bowel barrier function after ischemia/reperfusion injury in rats. Shock,2004,21:433-437.
Labow, B.I., Souba, W.W., Abcouwer, S.F. Mechanisms governing the expression of the enzymes of glutamine metabolism—glutaminase and glutamine synthetase. The Journal of Nutrition,2001,131:2467-2474.
Lackeyram, D., Yang, C.B., Archbold, T., Swanson, K.C., Fan, M.Z.,2010. Early weaning reduces small intestinal alkaline phosphatase expression in pigs. The Journal of Nutrition,140:461-468.
Li, M., Wang, B., Zhang, M., Rantalainen, M., Wang, S., Zhou, H., Zhang, Y, Shen, J., Pang, X., Zhang, M., Wei, H., Chen, Y., Lu. H., Zuo, J., Su, M., Qiu, Y., Jia, W., Xiao, C., Smith, L.M., Yang, S., Holmes, E., Tang. H., Zhao, G., Nicholson, J.K., Li, L., Zhao, L. Symbiotic gut microbes modulate human metabolic phenotypes. Proceedings of National Academy of Sciences of the United States of America, 2008,105:2117-2122.
Li, P., Yin. Y.L., Li, D., Kim, S.W., Wu, G. Amino acids and immune function. British Journal of Nutrition,2007,98:237-252.
Li, H.K., Ni, Y., Su, M.M., Qiu, Y.P., Zhou, M.M., Qiu, M.F., Zhao, A.H., Zhao, L.P., Jia, W. Pharmacometabonomic phenotyping reveals different responses to xenobiotic intervention in rats. Journal of Proteome Research,2007,6: 1364-1370.
Liao, X.H., Majithia, A., Huang, X.L., Kimmel, A.R. Growth control via TOR kinase signaling, an intracellular sensor of amino acid and energy availability, with crosstalk potential to proline metabolism. Amino Acids,2008,35:761-770.
Livak, K.J., Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-△△CT Method. Methods,2001,25:402-408.
Mateo, R.D., Wu, G., Bazer, F.W., Park, J.C., Shinzato, I., Kim, S.W. Dietary L-arginine supplementation enhances the reproductive performance of glits. The Journal of Nutrition,2007,137:652-656.
Maclennan, P.A., Smith, K., Weryk, B., Watt, P.W., Rennie, M.J. Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Letters,1988, 237:133-136.
Madej, M., Lundh, T., Lindberg, J.E. Activity of enzymes involved in energy production in the small intestine during suckling-weaning transition in pigs. Biology of Neonate,2002,82:53-60.
Madej, M., Lundh, T., Lindberg, J.E. Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets. Biology of Neonate,1999, 75:250-258.
Martin, F.P.J., Dumas, M.E., Wang, Y.L., Legido-Quigley, C., Yap, I.K.S., Tang, H.R. Zirah, S., Murphy, G.M., Cloarec, O., Lindon, J.C., Sprenger, N., Fay, L.B., Kochhar, S., van Bladeren, P., Holmes, E., Nicholson, J.K. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Molecular Systems Biology,2007,3:1-16.
Martin, F.P.J., Sprenger, N., Montoliu, I., Rezzi, S., Kochhar, S., Nicholson, J.K. Dietary Modulation of Gut Functional Ecology Studied by Fecal Metabonomics. Journal of Proteome Research,2010,9:5284-5295.
Meisse, D., Claeyssens, S., Husson, A. Lavoinne, A. Glutamine, a regulator of acute phase protein synthesis. Clinical Nutrition,1999,18:111-112.
Miller, B.G., James, P.S., Smith, M.W., Bourne F.J. Effect of weaning on the capacity of pig intestinal villi to digest and absorb nutrients. The Journal of Agricultural Science,1986,107:579-590.
Montagne, L., Boudry, G., Favier, C., Huerou-Luron, I.L., Lalles, J.P., Seve, B. Main intestinal markers associated with the changes in gut architecture and function in piglets after weaning. British Journal of Nutrition,2007,97:45-57.
Mountzouris, K.C., Fegeros, K., Papadopoulos, G. Utilization of fats based on the composition of sow milk fat in the diet of weanling pigs. Animal Feed Science and Technology,1999,77:115-124.
Murphy, J.M., Murch, S.J., Ball, R.O. Proline is synthesized from glutamate during intragastric infusion but not during intravenous infusion in neonatal piglets. The Journal of Nutrition,1996,126:878-886.
National Research Council.1998. Nutrient Requirements of Swine.10th Ed. National Academy Press, Washington, DC.
Newsholme, P., Brennnan, L., Rubi, B., Maechler, P. New insights into amino acid metabolism, beta-cell function and diabetes. Clinical Science,2005,108: 185-194.
Newsholme, E.A., Crabtree, B., Ardawi, M.S.M. The role of high rates of glycolysis and glutamine utilization in rapidly replication cells. Bioscience Reports,1985,4: 393-400.
Nelson, K.M., Long, C.L. Physiological basis for nutrition in sepsis. Nutrition in Clinical Practice,1989,4:6-15.
Nicholls, A.W., Mortishire-Smith, R.J., Nicholson, J.K. NMR Spectroscopic-Based Metabonomic Studies of Urinary Metabolite Variation in Acclimatizing Germ-Free Rats. Chemical Research in Toxicology,2003,16:1395-1404.
Nicholson, J.K., Lindon, J.C., Holmes, E.'Metabonomics':understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica,1999,29:1181-1189.
Nicholson, J.K., Holmes, E., Lindon, J.C., Wilson, I.D. The challenges of modeling mammalian biocomplexity. Nature Biotechnology,2004,22:1268-1274.
Nicholson, J.K., Lindon, J.C. System biology:metabonomics. Nature,2008,455: 1054-1056.
O'Connor, P.M.J., Kimball, S.R., Suryawan, A., Bush, J.A., Nguyen, H.V., Jefferson, L.S., Davis, T.A. Regulation of neonatal liver protein synthesis by insulin and amino acids in pigs. American Journal of Physiology Endocrinology and Metabolism.2004,286:994-1003.
Pacha, J. Development of intestinal transport function in mammals. Physiological Reviews,2000,80:1633-1667.
Panagiotou, G., Kouskoumvekaki, I., Jonsdottir, S.O., Olsson, L. Monitoring novel metabolic pathways using metabolomics and machine learning; induction of the phosphoketolase pathway in Aspergillus nidulans cultivations. Metabolomics, 2007,3:503-516.
Pedersen, L.L., Turco, S.J. Galactofuranose metabolism:a potential target for antimicrobial chemotherapy. Cellular and Molecular Life Sciences,2003,60: 259-266.
Peter, J.A.W., Jan, V.D.M., Martin, W.A.V. Intestinal barrier function and absorption in pigs after weaning:a review. British Journal of Nutrition,2011,105:967-981.
Petrovic, V., Novotny, J., Hisira, V., Link, R., Leng, E., Kovac, G. The impact of suckling and post-weaning period on blood chemistry of piglets. Acta Veterinaria Brno,2009,78:365-371.
Pie, S., Lalles, J.P., Blazy, F., Laffite, J., Seve, B., Oswald, I.P. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. The Journal of Nutrition,2004,134:641-647.
Qiao, Q., Li, T.H, Sun, J.M, Liu, X.Y, Ren, J.K, Fei, J. Metabolomic analysis of normal (C57BL/6J,129S1/SvlmJ) mice by gas chromatography-mass spectro-metry:Detection of strain and gender differences. Talanta,2011,85:718-724.
Quan, J., Fitch, M.D., Fleming, S.E. Rate at which glutamine enters TCA cycle influences carbon atom fate in intestinal epithelial cells. American Journal of Physiology Gastrointestinal and Liver Physiology,1998,275:1299-1308.
Reed, J.C. Bcl-2 family proteins. Oneogene,1998,17:3225-3236.
Reeds, P.J., Burrin, D.G. The gut and amino acid homeostasis. Nutrition,2000,16: 666-668.
Reeds, P.J., Burrin, D.G., Stoll, B., Jahoor, F. Intestinal glutamate metabolism. The Journal of Nutrition,2000,130:978-982.
Rezzi, S., Ramadan, Z., Fay, L.B., Kochhar, S. Nutritional metabonomics:applications and perspectives. Journal of Proteome Research,2007,6:513-525.
Rhoads, J.M., Wu, G.Y. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids,2009,37:111-122.
Riediger, N.D., Othman, R.A., Suh, M., Moghadasian, M.H. A systemic review of the roles of n-3 fatty acids in health and disease. Journal of the American Dietetic Association,2009,109:668-679.
Rider, J.E., Hacker, A, Mackintosh, C.A., Pegg, A. E., Woster, P.M., Casero, R.A. Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids,2007,33:231-240.
Rowan, E.M., Jennifer, K., Mary, K.D., Phillip, D.W. Biomarker discovery in animal health and disease:the application of post-genomic technologies. Biomarker Insights,2007.2:185-196.
Sangild, P.T., Cranwell. P.D., Sorensen, H., Nortensen, K., Noren, O., Wetteberg, L., Sjostrom, H. Develpmamt of intestinal disaccharideases, intestinal pepdases and pancreatic proteases in suckling pigs. The effects of age and ACTH treatment. In; Vertegen, M.W.A., Huisman, J. and Hartog (eds). Digestive Physiology in Pig. Pudoc. Wageningen,1991. pp:73-78.
Samuels, S.E., Aarts, H.L.M., Ball, R.O. Effect of dietary proline on proline metabolism in the neonatal pig. The Journal of Nutrition,1989,119:1900-1906.
Schmelzle, T., Hall, M.N. TOR, a central controller of cell growth. Cell,2000,103: 253-262.
Schnackenberg, L.K., Beger, R.D. Monitoring the health to disease continuum with global metabolic profiling and systems biology. Pharmacogenomics,2006,7: 1077-86.
Shikata, N., Maki, Y., Noguchi, Y., Mori, M., Hanai, T., Takahashi, M., Okamoto, M. Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition. Amino Acids,2007,33:113-121.
Skordi, E., Yap, I.K.S., Claus, S.P., Martin, F.P.J., Cloarec, O., Lindberg, J., Schuppe-Koistinen, I., Holmes, Elaine., Nicholson, J.K. Analysis of time-related metabolic fluctuations induced by ethionine in the rat. Journal of Proteome Research,2007,6:4572-4581.
Smith, F., Clark, J.E., Overman, B.L., Tozel, C.C., Huang, J.H., Rivier, J.E.F., Blisklager, A.T., Moeser, A.J. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. American Journal of Physiology Gastrointestinal and Liver Physiology,2010,298:352-363.
Sreekumar A., L. Poisson, M., Rajendiran, T.M., Khan, A.P., Cao, Q., Yu, J.D., Laxman, B., Mehra, R., R. Lonigro, J., Li, Y., Nyati, M.K.. Ahsan, A., Kalyana-Sundaram, S., Han, B., Cao, X., Byun, J., Omenn, G. S., Ghosh, D., Pennathur, S., Alexander, D. C., Berger, A., Shuster, J. R., Wei, J. T., Varambally, S., Beecher, C., Chinnaiyan, A.M. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature,2009,457:910-915.
Stein, H.H., Kim, S.W., Nielsen, T.T., Easter, R.A. Standardized ileal protein amino acid digestibility in growing pigs and sows. Journal of Animal Science,2001,79: 2113-2122.
Stifel, F.B., Herman, R.H., Rosensweig, N.S. Dietary regulation of glycolytic enzymes: III. Adaptive changes in rat jejunal pyruvate kinase, phosphofructokinase, fructose diphosphatase and glycerol-3-phosphate dehydrogenase. Biochimica et Biophysica Acta-General Subjects,1969,184:29-34.
Stoll, B., Burrin, D.G., Henry, J., Yu, H., Jahoor, F., Reeds, P.J. Substrate oxidation by the portal drained viscera of fed piglets. American Journal of Physiology Endocrinology Metabolism,1999,277:168-175.
Stumvoll M., Perriello, G., Meyer, C., Gerich, J. Role of glutamine in human carbohydrate metabolism in kidney and other tissues. Kidney International,1999, 55:778-792
Stumvoll, M., Meyer, C., Kreider, M., Perriello, G., Gerich, J. Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metabolism,1998,47:1227-1232.
Suryawan, A., Escobar, J., Frank, J.W., Nguyen, H.V., Davis, T.A. Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs. American Journal of Physiology Endocrinology and Metabolism,2006,291:849-859.
Tao, X.M., Liu, Y.M., Wang, Y.H., Qiu, Y.P., Lin, J.C., Zhao, A.H., Su, M.M., Jia, W. GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia. Analytical and Bioanalytical Chemistry,2008,391:2881-2889.
Taylor, J., King, R.D., Ahmann, T., Fiehn, O. Application of metabolomics to plant genotype discrimination using statistics and machine learning. Bioinformatics, 2002,18:241-248.
Tichelaar, H.Y. Possible relevance of abnormal fatty acid metabolism in undernutrition:the relationship between oleic acid and growth. Medical Hypotheses,2000,54:708-711.
Trygg, J., Holmes, E., Lundstedt, T. Chemometrics in metabonomics. Journal of Proteome Research,2007,6:469-479.
Vazquez, J.A., Daniel, H., Adibi, S.A. Dipeptide in parenteral nutrition:from basic to clinical applications. Nutrition in Clinical Practice,1993,17:47-55.
van Beers-Schreurs, H.M.G., Nabuurs, M.J.A., Vellenga, L., Kalsbeek, V.D, Valk, H.J. Wensing, T., Breukink, H.J. Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood. The Journal of Nutrition,1998,128:947-953.
van den Borne, J.J.G.C., WestrOm, B.R., Kruszewska, D., Botermans, J.A.M.. Svendsen, J., Wolinski, J., Pierzynowski, S.G. Exocrine pancreatic secretion in pigs fed sow's milk and milk replacer, and its relationship to growth performance. Journal of Animal Science,2007,85:404-412.
Valencia, D.G., Serrano, M.P., Lazaro, R., Jimenez-Moreno, E., Mateos, G.G. Influence of micronization (fine grinding) of soya bean meal and fullfat soya bean on productive performance and digestive traits in young pigs. Animal Feed Science and Technology,2008,147:340-356.
Vogtmann, H., Frirter, P., Prabuck, A.L. A new method of determining metabolizability of energy and digestibility of fatty acids in broiler diets. British Poultry Science,1975,16:531-534.
Wang, W.W, Qiao, S.Y, Li, D.F. Amino acids and gut function. Amino Acids,2008,37: 105-110.
Wang, J., Chen, L., Li, P., Li, X., Zhou, H., Wang, F., Li, D., Yin, Y., Wu, G. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. The Journal of Nutrition,2008,138:1025-1032.
Wang, Y., Lawler, D., Larson, B., Ramadan, Z., Kochhar, S., Holmes, E., Nicholson, J.K. Metabonomic investigations of aging and caloric restriction in a life-long dog study. Journal of Proteome Research,2007,6:1846-1854.
Wang, J.J., Wu, G.Y., Zhou, H.J., Wang, F.L. Emerging technologies for amino acid nutrition research in the post-genome era. Amino Acids,2008,37:177-186.
Wang, J., Qi, L., Zheng, S., Wu, T. Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells. Journal of Zhejiang University-Science B,2009,10:93-102.
Wang, X.Q., Ou, D.Y., Yin, J.D., Wu, G.Y., Wang, J.J. Proteomic analysis reveals altered expression of proteins related to glutathione metabolism and apoptosis in the small intestine of zinc oxide-supplemented piglets. Amino Acids,2009,37: 209-218.
Watford, M. Glutamine metabolism and function in relation to proline synthesis and the safety of glutamine and proline supplementation. The Journal of Nutrition, 2008,138:2003-2007.
Watford, M. Hepatic glutaminase expression:relationship to kidney-type glutaminase and to the urea cycle. The FASEB Journal,1993,7:1468-1474.
Wernerman, J. Clinical use of glutamine supplementation. The Journal of Nutrition, 2008,138:2040-2044.
White, L.W., Landau, B.R. Sugar transport and fructose metabolism in human intestine in vitro. The Journal of Clinical Investigation,1965,44:1200-1213.
Whitfield, P.D., German, A.J., Noble, P.M. Metabolomics:an emerging post-genomic tool for nutrition. British Journal of Nutrition,2004,2:549-555.
Windmueller, H.G., Spaeth, A.E. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. The Journal of Biological Chemistry,1978,253:69-76.
Windmueller, H.G., Speath, A.E. Uptake and metabolism of plasma glutamine by the small intestine. The Journal of Biological Chemistry,1974,249:5070-5079.
Wijtten, P. J., van der Meulen, J., Verstegen, M.W. Intestinal barrier function and absorption in pigs after weaning:a review. British Journal of Nutrition,2011,105: 967-981.
Wu, H., Xue, R., Dong, L., Liu, T., Deng, C., Zeng, H., Shen, X. Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Analytica Chimica Acta,2009,648:98-104.
Wu, G., Knabe, D.A. Free and protein-bound amino acids in sow's colostrums and milk. The Journal of Nutrition,1994,124:415-424.
Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R., Turner, N.D. Glutathione metabolism and its implications for health. The Journal of Nutrition,2004,134:489-492.
Wu, G.Y., Bazer, F.W., Davis, T.A., Jaeger, L.A., Johnson, G.A., Kim, S.W., Knabe, D.A., Meininger, C.J., Spencer, T.E., Yin, Y.L. Important roles for the arginine family of amino acids in swine nutrition and production. Livestock Science,2007, 112:8-22.
Wu, G., Bazer, F.W., Datta, S., Johnson, G.A., Li, P., Satterfield, M.C., Spencer, T.E. Proline metabolism in the conceptus:implications for fetal growth and development. Amino Acids,2008,35:691-702.
Wu, G.Y., Bazer, F.W., Davis. T.A., Kim. S.W., Li, P., Rhoads, J.M., Satterfield, M.C., Smith, S.B., Spencer, T.E., Yin, Y. Arginine metabolism and nutrition in growth, health and disease. Amino Acids,2009,37:153-168.
Wu, G., Bazer, F.W., Burghardt, R.C., Johnson, G.A., Kim, S.W., Knabe, D.A., Li, P., Li, X., McKnight. J.R., Satterfield, M.C., Spencer, T.E. Proline and hydroxyproline metabolism:implications for animal and human nutrition. Amino. Acids,2011,40:1053-1063.
Wu, G.Y., Borbolla, A.G., Knabe, D.A. The uptake of glutamine and release of arginine, citrulline and proline by the small intestine of developing pigs. The Journal of Nutrition,1994,124:2437-2444.
Wu, G.Y., Knabe, D.A, Yan, W., Flynn, N.E. Glutamine and glucose-metabolism in enterocytes of the neonatal pig. American Journal of Physiology,1995,268: 334-342.
Wu, G. Amino acids:metabolism, functions, and nutrition. Amino Acids,2009,37: 1-17.
Wu, G., Fang. Y.Z., Yang, S., Lupton, J.R., Turner, N.D. Glutathione metabolism and its implications for health. The Journal of Nutrition,2004.134:489-492.
Wu, G., Ott, T.L., Knabe, D.A., Bazer, F.W. Amino acid composition of the fetal pig. The Journal of Nutrition,1999,129:1031-1038.
Wu. G.Y., Meier. S.A., Knabe, D.A. Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. The Journal of Nutrition,1996,126:2578-2584.
Wu, G. Intestinal mucosal amino acid catabolism. The Journal of Nutrition,1998,128: 1249-52.
Wyss, M., Kaddurah-Daouk, R. Creatine and creatinine metabolism. Physiological Reviews,2000,80:1107-1213.
Xi, P.B., Jiang, Z.Y., Zheng, C.T., Lin, Y.C., Wu, G.Y. Regulation of protein metabolism by glutamine:implications for nutrition and health. Frontiers in Bioscience,2011,16:578-597.
Xiao, Y.P., Li, X.Y.. Wu, T.X., Yang, L.. Hong, Q.H., Yang, C.M., Chen, A.G. Effects of dietary glutamine supplementation on nutrient absorption and activity of enzymes involved in glutamine metabolism and energy production in the jejunum of weaned piglets. Journal of Animal and Veterinary Advances,2012,11: 1441-1449.
Xue, R.Y., Lin, Z.X., Deng, C.H., Dong, L., Liu, T.T, Wang, J.Y., and Shen, X.Z. A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22:3061-3068.
Young, V.R., Ajami, A.M. Glutamine:The emperor or his clothes? The Journal of Nutrition,2001,131:2449-2459.
Yuneva, M., Zamboni, N., Oefner, P. Sachidanandam, R., Lazebnik, Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. The Journal of Cell Biology,2007,178:93-105.
Zhang, F., Jia, Z., Gao, P., Kong, H., Li, X., Lu, X., Wu, Y., Xu, G. Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry. Molecular BioSystems,2010,6:852-861.
Zheng, X.T., Shen, J., Liu, Q., Wang, S.F., Cheng, Y.Y., Qu, H.B. Plasma fatty acids metabolic profiling analysis of coronary heart disease based on GC-MS and pattern recognition. Journal of Pharmaceutical and Biomedical Analysis,2009, 49:481-486.
Antonov, A.V., Dietmann, S., Mewes, H.W. KEGG spider:interpretation of genomics data in the context of the global gene metabolic network. Genome Biology,2008, 9:R179.
AOAC,2000. Official Methods of Analysis.17th edn. Association of Official Analytical Chemists, Arlington, Virginia.
Ardawi, M.S.M. Glutamine and glucose metabolism in human peripheral lymphocytesl. Metabolism,1988,37:99-103.
Barszcz, M. Skomial, J. The development of the small intestine of piglets-chosen aspects. Journal of Animal and Feed Sciences,2011,20:3-15.
Bazinet, R.P., McMillan, E.G., Seebaransingh, R., Hayes, A.M., Cunnane, S.C. Whole-body β-oxidation of 18:2ω6 and 18:3co3 in the pig varies marked ly with weaning strategy and dietary 18:3co3. Journal of Lipid Research,2003,44: 314-319.
Bertolo, R.F.P., Brunton, J.A., Pencharz, P.B., Ball, R.O. Arginine, ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs. American Journal of Physiology Endocrinology Metabolism,2003,284: 915-922.
Bertram, H.C., Hoppe, C., Petersen, B.O., Duus, J.O., Molgaard, C., Michaelsen, K.F. An NMR-based metabonomic investigation on effects of milk and meat protein diets given to 8-year-old boys. British Journal of Nutrition,2007,97:758-763.
Biener, G.P., Schjoerring, J.K., Jahn, T.P. Membrane transport of hydrogen peroxide. Biochimica et Biophysica Acta (BBA)-Biomembranes,2006,1758:994-1003.
Blachier, F., Claire, B., Bos, C., Tome, D. Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines.The American Journal of Clinical Nutrition,2009,90:814-821.
Board, M., Humm, S., Newsholme, E.A. Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochemical Journal,1990,262: 503-509.
Boza, J.J., Moennoz, D., Bournot, C.E., Blum, S., Zbinden, I., Finot, P.A., Ballevre, O. Role of glutamine on the de novo purine nucleotide synthesis in Caco-2 cells. European Journal of Nutrition,2000,39:38-46.
Breiman, L. Random Forests. Machine Learning,2001,45:5-32.
Brosnan, J.T., Wijekoon, E.P., Warford-Woolgar, L., Trottier, N.L., Brosnan, M.E., Brunton, J.A., Bertolo, R.F.P. Creatine synthesis is a major metabolic process in neonatal niglets and has important implications for amino acid metabolism and methyl balance. The Journal of Nutrition,2009,139:1292-1297.
Bruininx, E.M., Van der Peet-Schwering, C.M., Schrama, J.W., Vereijken, P.F., Vesseur, P.C., Everts, H., den Hartog, L.A., Beynen, A.C. Individually measured feed intake characteristics and growth performance of group-housed weanling pigs:effects of sex, initial body weight, and body weight distribution within groups. Journal of Animal Science,2001,79:301-308.
Cera, K.R., Mahan, D.C., Cross, R.F., Reinhart, G.A., Whitmoyer, R.E. Effect of age. weaning and postweaning diet on small intestinal growth and jejunal morphology in young swine. Journal of Animal Science,1988,66:574-584.
Cera, K.R., Mahan, D.C., Reinhart, G.A. Effect of weaning, week post-weaning and diet composition on pancreatic and small intestinal luminal lipase response in young swine. Journal of Animal Science,1990,68:384-391.
Chamorro, S., de Blas, C., Grant, G., Badiola, I., Menoyo, D., Carabano, R. Effect of dietary supplementation with glutamine and a combination of glutamine-arginine on intestinal health in 25-d-old weaned rabbits. Journal of Animal Science,2010, 88:170-180.
Chawla, A., Repa, J.J., Evans, R.M., Mangelsdorf, D.J. Nuclear receptors and lipid physiology:opening the X-files. Science,2001,294:1866-1870.
Chandra, J., Samali, A., Orrenius, S. Triggering and modulation of apoptosis by oxidative stress. Free Radical Biology and Medicine,2000,29:323-333.
Clowes, E.J., Aherne, F.X., Baracos, V.E. Skeletal muscle protein mobilization during the progression of lactation. American Journal of Physiology Endocrinology Metabolism,2004,288:E564-E572.
Coeffier, M., Claeyssens, S., Hecketsweiler, B., Lavoinne, A., Ducrotte, P., Dechelotte, P. Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa. American Journal of Physiology Gastrointestinal and Liver Physiology,2003,285:266-273.
Coss-Bu, J.A., Sunehag, A.L., Haymond, M.W. Contribution of galactose and fructose to glucose homeostasis. Metabolism,2009,58:1050-1058.
Curi, R., Lagranha, C.J., Doi, S.Q., Sellitti, D.F., Procopio, J., Pithon-Curi, T.C. Corless, M., Newsholme, P. Molecular mechanisms of glutamine action. Journal of Cellular Physiology,2005,204:392-401.
Darcy-Vrillon, B., Posho, L., Morell, M.T., Bernard, F., Blachier, F. Glucose, galactose, and glutamine metabolism in pig isolated enterocytes during development. Pediatric Research,1994,36:175-181.
Daykin, C.A., van Duynhoven, J.P.M., Groenewegen, A., Dachtler, M., Van Amelsvoort, J.M.M., Mulder, T.P.J. Nuclear magnetic resonance spectroscopic based studies of the metabolism of black tea polyphenols in humans. Journal of Agricultural and Food Chemistry,2005,53:1428-1434.
Deminice, R., Portari, G.V.,Vannucchi, H.,Jordao, A.A. Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats. British Journal of Nutrition,2009,102:110-116.
Denno, R., Rounds, J.D., Faris, R., Holejko, L.B., Wilmore, D.W. Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. Journal of Surgical Research,1996,61:35-38.
Dividich, J. L., Seve, B. Effects of underfeeding during the weaning period on growth, metabolism, and hormonal adjustments in the piglet. Domestic Animal Endocrinology,2000,19:63-74.
Evans, M.E., Jones, D.P., Ziegler, T.R. Glutamine Prevents Cytokine-Induced Apoptosis in Human Colonic Epithelial Cells. The Journal of Nutrition,2003, 133:3065-3071.
Fan, M.Z., Adeola, O., Asem, E.K., King, D. Postnatal ontogeny of kinetics of porcine jejunal brush border membrane-bound alkaline phosphatase, aminopeptidase N and sucrase activities. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology,2002,132:599-607.
Feng, B., Shiber, S.K. Max, S.R. Glutamine regulates glutamine synthetase expression in skeletal muscle cells in culture. Journal of Cellular Physiology,1990,145: 376-380.
Fiatte, C., Huin, C., Collet, P., Plenat, F., Dauca, M.,Schohn, H. Expression of PPARy is reduced by medium supplementation with L-glutamine in human colorectal Caco-2 cells. International Journal of Molecular Medicine,2008.22:825-832.
Fleming, S. E., Zambell, K. L., Fitch, M. D. Glucose and glutamine provide similar proportions of energy to mucosal cells of rat small intestine. American Journal of Physiology,1997,273:968-978.
Flynn. N.E., Knabe, D.A., Mallick, B.K., Wu, G. Postnatal changes of plasma amino acids in suckling pigs. Journal of Animal Science,2000,78:2369-2375.
Fujita, T., Yanaga, K. Association between glutamine extraction and release of citrulline and glycine by the human small intestine. Life Sciences,2007,80: 1846-1850.
Galli, A., Price, D., Crabb, D. High-level expression of rat class I alcohol dehydrogenase is sufficient for ethanol-induced fat accumulation in tranduced hela cells. Hepatology,1999,29:1164-1170.
Geddes, K., Philpott, D.J. A new role for intestinal alkaline phosphatase in gut barrier maintenance. Gastroenterology,2008,135:8-12.
Gong, J., Yu, H., Liu, T., Li, M., Si, W., de Lange, C.F.M., Dewey. C. Characterization of ileal bacterial microbiota in newly-weaned pigs in response to feeding lincomycin, organic acids or herbal extract. Livestock Science,2008,116: 318-322.
Grant, J. Use of L-glutamine in total parenteral nutrition. Journal of Surgical Research, 1998,44:506-513.
Guay, F., Trottier, N.L. Muscle growth and plasma concentrations of amino acids, insulin-like growth factor-I, and insulin in growing pigs fed reduced-protein diets. Journal of Animal Science,2006,84:3010-3019.
Gu, X., Li, D. Fat nutrition and metabolism in piglets:a review. Animal Feed Science and Technology,2003,109:151-170.
Gu, X., Li, D., She, R. Effect of weaning on small intestinal structure and function in the piglet. Archives of Animal Nutrition,2002,56:275-286.
Hammon, H., Blum, J.W. Prolonged colostrum feeding enhances xylose absorption in neonatal calves. Journal of Animal Science,1997,75:2915-2919.
Hampson, D.J., Kidder, D.E. Influence of creep feeding and weaning on brush borsh border enzyme activities in the piglet small intestine. Research in Veterinary Science,1986.40:24-31.
Hampson, D.J. Alteration in piglet small intestinal structure at weaning. Research in Veterinary Science,1986,40:32-40.
Haynes,T.E., Li, P., Li, X., Shimotori, K., Sato, H., Flynn, N.E., Wang, J., Knabe, D.A., Wu, G. L-Glutamine or L-alanyl-L-glutamine prevents oxidant-or endotoxin-induced death of neonatal enterocytes. Amino Acids,2009,37: 131-142.
He, Q., Ren, P., Kong, X., Wu, Y., Wu, G., Li, P., Hao, F., Tang, H., Blachier, F., Yin, Y. Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach. Journal of Nutritional Biochemistry,2012,23:133-139.
He. Q.H., Kong, X.F., Wu, G.Y., Ren, P.P., Tang, H.R., Hao, F.H., Huang, R.L., Li,T.J., Tan, B., Tang, Z.R., Yin, Y.L., Wu, Y.N. Metabolomic analysis of the response of growing pigs to dietary L-arginine supplementation. Amino Acids,2009,37: 199-208.
He, Q.H., Yin, Y.L., Zhao, F., Kong, X.F., Wu, G.Y., Ren, P.P. Metabonomics and its role in amino acid nutrition research. Frontiers in Bioscience,2011,16: 2451-2460.
Henning, S.J. Postnatal development:coordination of feeding, digestion, and metabolism. American Journal of Physiology Gastrointestinal and Liver Physiology,1981,24:199-214.
Hodin, R.A., Chamberlain, S.M., Meng, S. Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state. American Journal of Physiology Cell Physiology,1995,269:385-391.
Hubert-Buron, A., Leblond, J., Jacquot, A., Ducrotte, P., Dechelotte, P., Coiffier, M. Glutamine Pretreatment Reduces IL-8 Production in Human Intestinal Epithelial Cells by Limiting IκBα Ubiquitination. The Journal of Nutrition,2006,136: 1461-1465.
Hwang, J.J., Perera, S., Shapiro, R.A. Curthoys, Norman.P. Mechanism of altered renal glutaminase gene expression in response to chronic acidosis. Biochemistry, 1991,30:7522-7526.
Janczyk, P., Pieper, R., Smidt, H., Souffrant, W.B. Changes in the diversity of pig ileal lactobacilli around weaning determined by means of 16S rRNA gene amplification and denaturing gradient gel electrophoresis. FEMS Microbiology Ecology,2007,61:132-140.
Jia, Y., Lin, J., Mi, Y., Zhang, C. Quercetin attenuates cadmium-induced oxidative damage and apoptosis in granulosa cells from chicken ovarian follicles. Reproductive Toxicology,2011,31:477-485.
Jobgen, W.S., Fried, S.K., Fu, W.J., Meininger, C.J., Wu, G. Regulatory role for the arginine-nitric oxide pathway in energy-substrate metabolism. The Journal of Nutritional Biochemistry,2006,17:571-588.
Jones, D.P. Radical-free biology of oxidative stress. American Journal of Physiology Cell Physiology,2008,295:C849-C868.
Kim, S.W., Wu, G. Dietary arginine supplementation enhances the growth of milk-fed young pigs. The Journal of Nutrition,2004,134:625-630.
Kimball, S.R., Jefferson, L.S., Nguyen, H.V., Suryawan, A., Bush, J.A., Davis, T.A. Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process. American Journal of Physiology Endocrinology and Metabolism,2000,279:1080-1087.
Kirchgessner, M., Fickler, J., Roth, F.X. Effect of dietary proline supply on N-balance of piglets.3. Communication on the importance of nonessential amino acids for protein retention. Journal of Animal Physiology and Animal Nutrition,1995,73: 57-65.
Kong, X.F., Yin, Y.L., He, Q.H., Yin, F.G., Liu, H.J., Li, T.J., Huang, R.L., Geng, M.M., Ruan, Z., Deng, Z.Y., Xie, M.Y., Wu, G. Dietary supplementation with Chinese herbal powder enhances ileal digestibilities and serum concentrations of amino acids in young pigs. Amino Acids,2009,37:573-582.
Kozar, R.A., Schultz, S.G., Bick, R.J., Poindexter, B.J., DeSoignie, R., Moore, F.A. Enteral glutamine but not alanine maintains small bowel barrier function after ischemia/reperfusion injury in rats. Shock,2004,21:433-437.
Labow, B.I., Souba, W.W., Abcouwer, S.F. Mechanisms governing the expression of the enzymes of glutamine metabolism—glutaminase and glutamine synthetase. The Journal of Nutrition,2001,131:2467-2474.
Lackeyram, D., Yang, C.B., Archbold, T., Swanson, K.C., Fan, M.Z.,2010. Early weaning reduces small intestinal alkaline phosphatase expression in pigs. The Journal of Nutrition,140:461-468.
Li, M., Wang, B., Zhang, M., Rantalainen, M., Wang, S., Zhou, H., Zhang, Y, Shen, J., Pang, X., Zhang, M., Wei, H., Chen, Y., Lu. H., Zuo, J., Su, M., Qiu, Y., Jia, W., Xiao, C., Smith, L.M., Yang, S., Holmes, E., Tang. H., Zhao, G., Nicholson, J.K., Li, L., Zhao, L. Symbiotic gut microbes modulate human metabolic phenotypes. Proceedings of National Academy of Sciences of the United States of America, 2008,105:2117-2122.
Li, P., Yin. Y.L., Li, D., Kim, S.W., Wu, G. Amino acids and immune function. British Journal of Nutrition,2007,98:237-252.
Li, H.K., Ni, Y., Su, M.M., Qiu, Y.P., Zhou, M.M., Qiu, M.F., Zhao, A.H., Zhao, L.P., Jia, W. Pharmacometabonomic phenotyping reveals different responses to xenobiotic intervention in rats. Journal of Proteome Research,2007,6: 1364-1370.
Liao, X.H., Majithia, A., Huang, X.L., Kimmel, A.R. Growth control via TOR kinase signaling, an intracellular sensor of amino acid and energy availability, with crosstalk potential to proline metabolism. Amino Acids,2008,35:761-770.
Livak, K.J., Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-△△CT Method. Methods,2001,25:402-408.
Mateo, R.D., Wu, G., Bazer, F.W., Park, J.C., Shinzato, I., Kim, S.W. Dietary L-arginine supplementation enhances the reproductive performance of glits. The Journal of Nutrition,2007,137:652-656.
Maclennan, P.A., Smith, K., Weryk, B., Watt, P.W., Rennie, M.J. Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Letters,1988, 237:133-136.
Madej, M., Lundh, T., Lindberg, J.E. Activity of enzymes involved in energy production in the small intestine during suckling-weaning transition in pigs. Biology of Neonate,2002,82:53-60.
Madej, M., Lundh, T., Lindberg, J.E. Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets. Biology of Neonate,1999, 75:250-258.
Martin, F.P.J., Dumas, M.E., Wang, Y.L., Legido-Quigley, C., Yap, I.K.S., Tang, H.R. Zirah, S., Murphy, G.M., Cloarec, O., Lindon, J.C., Sprenger, N., Fay, L.B., Kochhar, S., van Bladeren, P., Holmes, E., Nicholson, J.K. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Molecular Systems Biology,2007,3:1-16.
Martin, F.P.J., Sprenger, N., Montoliu, I., Rezzi, S., Kochhar, S., Nicholson, J.K. Dietary Modulation of Gut Functional Ecology Studied by Fecal Metabonomics. Journal of Proteome Research,2010,9:5284-5295.
Meisse, D., Claeyssens, S., Husson, A. Lavoinne, A. Glutamine, a regulator of acute phase protein synthesis. Clinical Nutrition,1999,18:111-112.
Miller, B.G., James, P.S., Smith, M.W., Bourne F.J. Effect of weaning on the capacity of pig intestinal villi to digest and absorb nutrients. The Journal of Agricultural Science,1986,107:579-590.
Montagne, L., Boudry, G., Favier, C., Huerou-Luron, I.L., Lalles, J.P., Seve, B. Main intestinal markers associated with the changes in gut architecture and function in piglets after weaning. British Journal of Nutrition,2007,97:45-57.
Mountzouris, K.C., Fegeros, K., Papadopoulos, G. Utilization of fats based on the composition of sow milk fat in the diet of weanling pigs. Animal Feed Science and Technology,1999,77:115-124.
Murphy, J.M., Murch, S.J., Ball, R.O. Proline is synthesized from glutamate during intragastric infusion but not during intravenous infusion in neonatal piglets. The Journal of Nutrition,1996,126:878-886.
National Research Council.1998. Nutrient Requirements of Swine.10th Ed. National Academy Press, Washington, DC.
Newsholme, P., Brennnan, L., Rubi, B., Maechler, P. New insights into amino acid metabolism, beta-cell function and diabetes. Clinical Science,2005,108: 185-194.
Newsholme, E.A., Crabtree, B., Ardawi, M.S.M. The role of high rates of glycolysis and glutamine utilization in rapidly replication cells. Bioscience Reports,1985,4: 393-400.
Nelson, K.M., Long, C.L. Physiological basis for nutrition in sepsis. Nutrition in Clinical Practice,1989,4:6-15.
Nicholls, A.W., Mortishire-Smith, R.J., Nicholson, J.K. NMR Spectroscopic-Based Metabonomic Studies of Urinary Metabolite Variation in Acclimatizing Germ-Free Rats. Chemical Research in Toxicology,2003,16:1395-1404.
Nicholson, J.K., Lindon, J.C., Holmes, E.'Metabonomics':understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica,1999,29:1181-1189.
Nicholson, J.K., Holmes, E., Lindon, J.C., Wilson, I.D. The challenges of modeling mammalian biocomplexity. Nature Biotechnology,2004,22:1268-1274.
Nicholson, J.K., Lindon, J.C. System biology:metabonomics. Nature,2008,455: 1054-1056.
O'Connor, P.M.J., Kimball, S.R., Suryawan, A., Bush, J.A., Nguyen, H.V., Jefferson, L.S., Davis, T.A. Regulation of neonatal liver protein synthesis by insulin and amino acids in pigs. American Journal of Physiology Endocrinology and Metabolism.2004,286:994-1003.
Pacha, J. Development of intestinal transport function in mammals. Physiological Reviews,2000,80:1633-1667.
Panagiotou, G., Kouskoumvekaki, I., Jonsdottir, S.O., Olsson, L. Monitoring novel metabolic pathways using metabolomics and machine learning; induction of the phosphoketolase pathway in Aspergillus nidulans cultivations. Metabolomics, 2007,3:503-516.
Pedersen, L.L., Turco, S.J. Galactofuranose metabolism:a potential target for antimicrobial chemotherapy. Cellular and Molecular Life Sciences,2003,60: 259-266.
Peter, J.A.W., Jan, V.D.M., Martin, W.A.V. Intestinal barrier function and absorption in pigs after weaning:a review. British Journal of Nutrition,2011,105:967-981.
Petrovic, V., Novotny, J., Hisira, V., Link, R., Leng, E., Kovac, G. The impact of suckling and post-weaning period on blood chemistry of piglets. Acta Veterinaria Brno,2009,78:365-371.
Pie, S., Lalles, J.P., Blazy, F., Laffite, J., Seve, B., Oswald, I.P. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. The Journal of Nutrition,2004,134:641-647.
Qiao, Q., Li, T.H, Sun, J.M, Liu, X.Y, Ren, J.K, Fei, J. Metabolomic analysis of normal (C57BL/6J,129S1/SvlmJ) mice by gas chromatography-mass spectro-metry:Detection of strain and gender differences. Talanta,2011,85:718-724.
Quan, J., Fitch, M.D., Fleming, S.E. Rate at which glutamine enters TCA cycle influences carbon atom fate in intestinal epithelial cells. American Journal of Physiology Gastrointestinal and Liver Physiology,1998,275:1299-1308.
Reed, J.C. Bcl-2 family proteins. Oneogene,1998,17:3225-3236.
Reeds, P.J., Burrin, D.G. The gut and amino acid homeostasis. Nutrition,2000,16: 666-668.
Reeds, P.J., Burrin, D.G., Stoll, B., Jahoor, F. Intestinal glutamate metabolism. The Journal of Nutrition,2000,130:978-982.
Rezzi, S., Ramadan, Z., Fay, L.B., Kochhar, S. Nutritional metabonomics:applications and perspectives. Journal of Proteome Research,2007,6:513-525.
Rhoads, J.M., Wu, G.Y. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids,2009,37:111-122.
Riediger, N.D., Othman, R.A., Suh, M., Moghadasian, M.H. A systemic review of the roles of n-3 fatty acids in health and disease. Journal of the American Dietetic Association,2009,109:668-679.
Rider, J.E., Hacker, A, Mackintosh, C.A., Pegg, A. E., Woster, P.M., Casero, R.A. Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids,2007,33:231-240.
Rowan, E.M., Jennifer, K., Mary, K.D., Phillip, D.W. Biomarker discovery in animal health and disease:the application of post-genomic technologies. Biomarker Insights,2007.2:185-196.
Sangild, P.T., Cranwell. P.D., Sorensen, H., Nortensen, K., Noren, O., Wetteberg, L., Sjostrom, H. Develpmamt of intestinal disaccharideases, intestinal pepdases and pancreatic proteases in suckling pigs. The effects of age and ACTH treatment. In; Vertegen, M.W.A., Huisman, J. and Hartog (eds). Digestive Physiology in Pig. Pudoc. Wageningen,1991. pp:73-78.
Samuels, S.E., Aarts, H.L.M., Ball, R.O. Effect of dietary proline on proline metabolism in the neonatal pig. The Journal of Nutrition,1989,119:1900-1906.
Schmelzle, T., Hall, M.N. TOR, a central controller of cell growth. Cell,2000,103: 253-262.
Schnackenberg, L.K., Beger, R.D. Monitoring the health to disease continuum with global metabolic profiling and systems biology. Pharmacogenomics,2006,7: 1077-86.
Shikata, N., Maki, Y., Noguchi, Y., Mori, M., Hanai, T., Takahashi, M., Okamoto, M. Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition. Amino Acids,2007,33:113-121.
Skordi, E., Yap, I.K.S., Claus, S.P., Martin, F.P.J., Cloarec, O., Lindberg, J., Schuppe-Koistinen, I., Holmes, Elaine., Nicholson, J.K. Analysis of time-related metabolic fluctuations induced by ethionine in the rat. Journal of Proteome Research,2007,6:4572-4581.
Smith, F., Clark, J.E., Overman, B.L., Tozel, C.C., Huang, J.H., Rivier, J.E.F., Blisklager, A.T., Moeser, A.J. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. American Journal of Physiology Gastrointestinal and Liver Physiology,2010,298:352-363.
Sreekumar A., L. Poisson, M., Rajendiran, T.M., Khan, A.P., Cao, Q., Yu, J.D., Laxman, B., Mehra, R., R. Lonigro, J., Li, Y., Nyati, M.K.. Ahsan, A., Kalyana-Sundaram, S., Han, B., Cao, X., Byun, J., Omenn, G. S., Ghosh, D., Pennathur, S., Alexander, D. C., Berger, A., Shuster, J. R., Wei, J. T., Varambally, S., Beecher, C., Chinnaiyan, A.M. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature,2009,457:910-915.
Stein, H.H., Kim, S.W., Nielsen, T.T., Easter, R.A. Standardized ileal protein amino acid digestibility in growing pigs and sows. Journal of Animal Science,2001,79: 2113-2122.
Stifel, F.B., Herman, R.H., Rosensweig, N.S. Dietary regulation of glycolytic enzymes: III. Adaptive changes in rat jejunal pyruvate kinase, phosphofructokinase, fructose diphosphatase and glycerol-3-phosphate dehydrogenase. Biochimica et Biophysica Acta-General Subjects,1969,184:29-34.
Stoll, B., Burrin, D.G., Henry, J., Yu, H., Jahoor, F., Reeds, P.J. Substrate oxidation by the portal drained viscera of fed piglets. American Journal of Physiology Endocrinology Metabolism,1999,277:168-175.
Stumvoll M., Perriello, G., Meyer, C., Gerich, J. Role of glutamine in human carbohydrate metabolism in kidney and other tissues. Kidney International,1999, 55:778-792
Stumvoll, M., Meyer, C., Kreider, M., Perriello, G., Gerich, J. Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metabolism,1998,47:1227-1232.
Suryawan, A., Escobar, J., Frank, J.W., Nguyen, H.V., Davis, T.A. Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs. American Journal of Physiology Endocrinology and Metabolism,2006,291:849-859.
Tao, X.M., Liu, Y.M., Wang, Y.H., Qiu, Y.P., Lin, J.C., Zhao, A.H., Su, M.M., Jia, W. GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia. Analytical and Bioanalytical Chemistry,2008,391:2881-2889.
Taylor, J., King, R.D., Ahmann, T., Fiehn, O. Application of metabolomics to plant genotype discrimination using statistics and machine learning. Bioinformatics, 2002,18:241-248.
Tichelaar, H.Y. Possible relevance of abnormal fatty acid metabolism in undernutrition:the relationship between oleic acid and growth. Medical Hypotheses,2000,54:708-711.
Trygg, J., Holmes, E., Lundstedt, T. Chemometrics in metabonomics. Journal of Proteome Research,2007,6:469-479.
Vazquez, J.A., Daniel, H., Adibi, S.A. Dipeptide in parenteral nutrition:from basic to clinical applications. Nutrition in Clinical Practice,1993,17:47-55.
van Beers-Schreurs, H.M.G., Nabuurs, M.J.A., Vellenga, L., Kalsbeek, V.D, Valk, H.J. Wensing, T., Breukink, H.J. Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood. The Journal of Nutrition,1998,128:947-953.
van den Borne, J.J.G.C., WestrOm, B.R., Kruszewska, D., Botermans, J.A.M.. Svendsen, J., Wolinski, J., Pierzynowski, S.G. Exocrine pancreatic secretion in pigs fed sow's milk and milk replacer, and its relationship to growth performance. Journal of Animal Science,2007,85:404-412.
Valencia, D.G., Serrano, M.P., Lazaro, R., Jimenez-Moreno, E., Mateos, G.G. Influence of micronization (fine grinding) of soya bean meal and fullfat soya bean on productive performance and digestive traits in young pigs. Animal Feed Science and Technology,2008,147:340-356.
Vogtmann, H., Frirter, P., Prabuck, A.L. A new method of determining metabolizability of energy and digestibility of fatty acids in broiler diets. British Poultry Science,1975,16:531-534.
Wang, W.W, Qiao, S.Y, Li, D.F. Amino acids and gut function. Amino Acids,2008,37: 105-110.
Wang, J., Chen, L., Li, P., Li, X., Zhou, H., Wang, F., Li, D., Yin, Y., Wu, G. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. The Journal of Nutrition,2008,138:1025-1032.
Wang, Y., Lawler, D., Larson, B., Ramadan, Z., Kochhar, S., Holmes, E., Nicholson, J.K. Metabonomic investigations of aging and caloric restriction in a life-long dog study. Journal of Proteome Research,2007,6:1846-1854.
Wang, J.J., Wu, G.Y., Zhou, H.J., Wang, F.L. Emerging technologies for amino acid nutrition research in the post-genome era. Amino Acids,2008,37:177-186.
Wang, J., Qi, L., Zheng, S., Wu, T. Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells. Journal of Zhejiang University-Science B,2009,10:93-102.
Wang, X.Q., Ou, D.Y., Yin, J.D., Wu, G.Y., Wang, J.J. Proteomic analysis reveals altered expression of proteins related to glutathione metabolism and apoptosis in the small intestine of zinc oxide-supplemented piglets. Amino Acids,2009,37: 209-218.
Watford, M. Glutamine metabolism and function in relation to proline synthesis and the safety of glutamine and proline supplementation. The Journal of Nutrition, 2008,138:2003-2007.
Watford, M. Hepatic glutaminase expression:relationship to kidney-type glutaminase and to the urea cycle. The FASEB Journal,1993,7:1468-1474.
Wernerman, J. Clinical use of glutamine supplementation. The Journal of Nutrition, 2008,138:2040-2044.
White, L.W., Landau, B.R. Sugar transport and fructose metabolism in human intestine in vitro. The Journal of Clinical Investigation,1965,44:1200-1213.
Whitfield, P.D., German, A.J., Noble, P.M. Metabolomics:an emerging post-genomic tool for nutrition. British Journal of Nutrition,2004,2:549-555.
Windmueller, H.G., Spaeth, A.E. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. The Journal of Biological Chemistry,1978,253:69-76.
Windmueller, H.G., Speath, A.E. Uptake and metabolism of plasma glutamine by the small intestine. The Journal of Biological Chemistry,1974,249:5070-5079.
Wijtten, P. J., van der Meulen, J., Verstegen, M.W. Intestinal barrier function and absorption in pigs after weaning:a review. British Journal of Nutrition,2011,105: 967-981.
Wu, H., Xue, R., Dong, L., Liu, T., Deng, C., Zeng, H., Shen, X. Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Analytica Chimica Acta,2009,648:98-104.
Wu, G., Knabe, D.A. Free and protein-bound amino acids in sow's colostrums and milk. The Journal of Nutrition,1994,124:415-424.
Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R., Turner, N.D. Glutathione metabolism and its implications for health. The Journal of Nutrition,2004,134:489-492.
Wu, G.Y., Bazer, F.W., Davis, T.A., Jaeger, L.A., Johnson, G.A., Kim, S.W., Knabe, D.A., Meininger, C.J., Spencer, T.E., Yin, Y.L. Important roles for the arginine family of amino acids in swine nutrition and production. Livestock Science,2007, 112:8-22.
Wu, G., Bazer, F.W., Datta, S., Johnson, G.A., Li, P., Satterfield, M.C., Spencer, T.E. Proline metabolism in the conceptus:implications for fetal growth and development. Amino Acids,2008,35:691-702.
Wu, G.Y., Bazer, F.W., Davis. T.A., Kim. S.W., Li, P., Rhoads, J.M., Satterfield, M.C., Smith, S.B., Spencer, T.E., Yin, Y. Arginine metabolism and nutrition in growth, health and disease. Amino Acids,2009,37:153-168.
Wu, G., Bazer, F.W., Burghardt, R.C., Johnson, G.A., Kim, S.W., Knabe, D.A., Li, P., Li, X., McKnight. J.R., Satterfield, M.C., Spencer, T.E. Proline and hydroxyproline metabolism:implications for animal and human nutrition. Amino. Acids,2011,40:1053-1063.
Wu, G.Y., Borbolla, A.G., Knabe, D.A. The uptake of glutamine and release of arginine, citrulline and proline by the small intestine of developing pigs. The Journal of Nutrition,1994,124:2437-2444.
Wu, G.Y., Knabe, D.A, Yan, W., Flynn, N.E. Glutamine and glucose-metabolism in enterocytes of the neonatal pig. American Journal of Physiology,1995,268: 334-342.
Wu, G. Amino acids:metabolism, functions, and nutrition. Amino Acids,2009,37: 1-17.
Wu, G., Fang. Y.Z., Yang, S., Lupton, J.R., Turner, N.D. Glutathione metabolism and its implications for health. The Journal of Nutrition,2004.134:489-492.
Wu, G., Ott, T.L., Knabe, D.A., Bazer, F.W. Amino acid composition of the fetal pig. The Journal of Nutrition,1999,129:1031-1038.
Wu. G.Y., Meier. S.A., Knabe, D.A. Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. The Journal of Nutrition,1996,126:2578-2584.
Wu, G. Intestinal mucosal amino acid catabolism. The Journal of Nutrition,1998,128: 1249-52.
Wyss, M., Kaddurah-Daouk, R. Creatine and creatinine metabolism. Physiological Reviews,2000,80:1107-1213.
Xi, P.B., Jiang, Z.Y., Zheng, C.T., Lin, Y.C., Wu, G.Y. Regulation of protein metabolism by glutamine:implications for nutrition and health. Frontiers in Bioscience,2011,16:578-597.
Xiao, Y.P., Li, X.Y.. Wu, T.X., Yang, L.. Hong, Q.H., Yang, C.M., Chen, A.G. Effects of dietary glutamine supplementation on nutrient absorption and activity of enzymes involved in glutamine metabolism and energy production in the jejunum of weaned piglets. Journal of Animal and Veterinary Advances,2012,11: 1441-1449.
Xue, R.Y., Lin, Z.X., Deng, C.H., Dong, L., Liu, T.T, Wang, J.Y., and Shen, X.Z. A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22:3061-3068.
Young, V.R., Ajami, A.M. Glutamine:The emperor or his clothes? The Journal of Nutrition,2001,131:2449-2459.
Yuneva, M., Zamboni, N., Oefner, P. Sachidanandam, R., Lazebnik, Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. The Journal of Cell Biology,2007,178:93-105.
Zhang, F., Jia, Z., Gao, P., Kong, H., Li, X., Lu, X., Wu, Y., Xu, G. Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry. Molecular BioSystems,2010,6:852-861.
Zheng, X.T., Shen, J., Liu, Q., Wang, S.F., Cheng, Y.Y., Qu, H.B. Plasma fatty acids metabolic profiling analysis of coronary heart disease based on GC-MS and pattern recognition. Journal of Pharmaceutical and Biomedical Analysis,2009, 49:481-486.