Dietary L-glutamine Supplementation Research Articles

Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with β-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-β in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Effect of dietary l-glutamine supplementation on the intestinal physiology and growth during Solea senegalensis larval development

The maturation of the intestinal digestive and absorptive functions might limit the amount of absorbed nutrients to fulfil the high requirements of the fast-growing marine fish larva. Glutamine (Gln) has been described to improve intestinal epithelium functions, due to its involvement in energy metabolism and protein synthesis. The purpose of this study was to evaluate dietary 0.2% Gln supplementation on aspects of intestinal physiology, protein metabolism and growth-related genes expression in Senegalese sole larvae. Experiment was carried out between 12 and 33 days post hatching (DPH) and fish were divided into two experimental groups, one fed Artemia spp. (CTRL) and the other fed Artemia spp. supplemented with Gln (GLN). GLN diet had two times more Gln than the CTRL diet. Samples were collected at 15, 19, 26 and 33 DPH for biometry, histology, and digestive enzymes activity, and at 33 DPH for gene expression, protein metabolism and AA content determination. Growth was significantly higher for Senegalese sole fed GLN diet, supported by differences on protein metabolism and growth-related gene expression. Slight differences were observed between treatments regarding the intestinal physiology. Overall, GLN diet seems to be directed to enhance protein metabolism leading to higher larval growth.

The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease

BackgroundTaurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation.MethodsCKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet.ResultsTaurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05).ConclusionIn CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.

Impact of L-glutamine as replacement of dietary antibiotics during post weaning and transport recovery on carcass and meat quality attributes in pigs

Dietary L-glutamine could be used as an antibiotic alternative to alleviate post-weaning and transport stress. However, the impact of supplementing L-glutamine to newly weaned and transported pigs on final carcass and meat quality characteristics is currently unknown. Therefore, the objective of this study was to evaluate the impact of 0.2% dietary L-glutamine supplementation during post-weaning and transport recovery on carcass and meat quality attributes in pigs. A total of 480 mixed-sex pigs were studied in two production seasons, July-January and April-September (from weaning to harvest), where pigs were randomly assigned to 3 different diets (Non: no antibiotic, Anti: 441 ppm chlortetracycline and 38.6 ppm tiamulin, Gln: 0.20% L-glutamine with no antibiotics) for 14 days after weaning and transport, and then all pigs were fed a basal diet until reaching market weight. Pairs of longissimus dorsi (LD) and psoas major (PM) muscles were obtained from 1 d and 7 d postmortem carcass sides (n = 10 gilts/dietary treatment/season replicate). Overall, no negative impacts of Gln were observed in carcass characteristics including loin eye area, back fat, and muscling score. Dietary Gln did not affect chemical and physical attributes of porcine muscles including pH, protein and lipid content, SF, and WHC (P > 0.05). The Gln treated pigs had decreased CIE L* and hue, suggesting enhanced color stability. April-September replicates had a faster pH decline, paler surface color, higher intra-muscular fat deposition, improved tenderness and water-holding capacity as indicated by lower shear force values, thaw-purge loss, and cooking loss compared to their July-January counterparts (P < 0.05). These results suggested that L-glutamine supplementation as a nutraceutical mitigation strategy could have equivalent impacts on fat and lean accretion, SF, and WHC and some positive impacts on meat color attributes compared to meat from pigs treated with antibiotics.

Dietary L-glutamine supplementation improves growth performance, gut morphology, and serum biochemical indices of broiler chickens during necrotic enteritis challenge

Necrotic enteritis (NE) causes significant economic losses in the broiler chicken industry, especially in birds raised without in-feed antibiotics. L-glutamine (Gln) is an amino acid that may compensate for metabolic losses from infection and improve the intestinal development. This study investigated the effects of dietary Gln (10g/kg) supplementation on growth performance, intestinal lesions, jejunum morphology, and serum biochemical indices of broiler chickens during NE challenge. The study employed a factorial arrangement of treatments with factors: NE challenge, no or yes; dietary Gln inclusion, 0g/kg in starter (S), d 0 to 10, grower (G) d 10 to 24, and finisher (F) d 24 to 35; 10g/kg in S, G, F, or 10g/kg in S, G only. Each treatment was replicated in 6 floor pens with 17 birds per pen as the experimental unit for performance and 2 birds for other measurements. Challenge significantly reduced bird performance, increased incidence of intestinal lesions, and affected intestinal development and serum biochemical indices. Regardless of challenge, Gln supplementation increased gain (P < 0.05), feed intake (P < 0.05), and decreased FCR (P < 0.05) on d 24. On d 35, Gln improved gain (P < 0.05) and FCR (P < 0.001) whereas withdrawing Gln from finisher tended to diminish the beneficial effect on weight gain but not FCR. Dietary Gln reduced lesion scores in the jejunum (P < 0.01) and ileum (P < 0.01) in challenged birds. On d 16, Gln increased villus height to crypt depth ratio in unchallenged birds (P < 0.05) and reduced crypt depth of challenged birds on d 24 (P < 0.05). Regardless of challenge, supplementation with Gln reduced crypt depth on d 16 (P < 0.05), and increased villus height (P < 0.01) and the villus height to crypt depth ratio (P < 0.001) on d 24. Dietary Gln lowered serum uric acid level regardless of challenge (P < 0.05). The current study indicates that dietary Gln alleviates adverse effects of NE and may be useful in antibiotic-free diets.

Dietary L-glutamine supplementation modulates microbial community and activates innate immunity in the mouse intestine.

This study was conducted to determine effects of dietary supplementation with 1 % L-glutamine for 14 days on the abundance of intestinal bacteria and the activation of intestinal innate immunity in mice. The measured variables included (1) the abundance of Bacteroidetes, Firmicutes, Lactobacillus, Streptococcus and Bifidobacterium in the lumen of the small intestine; (2) the expression of toll-like receptors (TLRs), pro-inflammatory cytokines, and antibacterial substances secreted by Paneth cells and goblet cells in the jejunum, ileum and colon; and (3) the activation of TLR4-nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), and phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt) signaling pathways in the jejunum and ileum. In the jejunum, glutamine supplementation decreased the abundance of Firmicutes, while increased mRNA levels for antibacterial substances in association with the activation of NF-κB and PI3K-Akt pathways. In the ileum, glutamine supplementation induced a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes, and enhanced mRNA levels for Tlr4, pro-inflammatory cytokines, and antibacterial substances participating in NF-κB and JNK signaling pathways. These results indicate that the effects of glutamine on the intestine vary with its segments and compartments. Collectively, dietary glutamine supplementation of mice beneficially alters intestinal bacterial community and activates the innate immunity in the small intestine through NF-κB, MAPK and PI3K-Akt signaling pathways.

Dietary l-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice

This study was conducted to determine the effects of graded doses of L-glutamine supplementation on the replication and distribution of Pasteurella multocida, and the expression of its major virulence factors in mouse model. Mice were randomly assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0% glutamine. Pasteurella multocida burden was detected in the heart, liver, spleen, lung and kidney after 12h of P. multocida infection. The expression of major virulence factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5% glutamine supplementation has little significant effect on these parameters, compared to those with basal diet. However, results showed that a high dose of glutamine supplementation increased the P. multocida burden (P<0.001) and the expression of its major virulence factors (P<0.05) as compared to those with a lower dose of supplementation. In the lung, high dose of glutamine supplementation inhibited the proinflammatory responses (P<0.05) and TLRs signaling (P<0.05). In the spleen, the effect of glutamine supplementation on different components in TLR signaling depends on glutamine concentration, and high dose of glutamine supplementation activated the proinflammatory response. In conclusion, glutamine supplementation increased P. multocida burden and the expression of its major virulence factors, while affecting the functions of the lung and spleen.

Improved performance and small intestinal development of broiler chickens by dietary L-glutamine supplementation

An experiment was conducted to evaluate the effect of L-glutamine (Gln) supplementation on performance and intestinal morphology of broiler chickens. A total of 192 day-old male broilers (Ross 308) were used in a completely randomised design with four treatments and four replicates of 12 birds each. Four experimental diets were formulated to be isonitrogenous and isocaloric with different levels of Gln supplementation (0, 0.5, 1.0 and 1.5%) in control and treatment groups, respectively and were fed for the first 3 weeks of life. On days 21 and 42, one bird from each replicate was slaughtered and morphometric indices of the small intestine were evaluated. Results obtained on days 21 and 42 showed increased ADWG in the birds that consumed 1% Gln supplemented diet compared to the control birds fed a standard corn-SBM diet (P≤0.05). On day 21, birds fed diets supplemented with 1 or 1.5% Gln had a significantly heavier duodenum and jejunum relative weight compared to the control birds (P≤0.05). Morphological assays showed that villus height and villus surface area of the duodenum and jejunum were significantly increased at both 21 and 42 days of age, as 1 or 1.5% Gln was supplemented in broiler diets (P≤0.05). The results of this study indicated that addition of 1% Gln to the diet for 21 days improved growth performance and small intestinal development of broiler chickens at the end of the starter (day 21) and grower (day 42) period.

Response to dietary L-glutamine supplementation in weaned piglets: a serum metabolomic comparison and hepatic metabolic regulation analysis

Response to dietary L-glutamine supplementation in weaned piglets: a serum metabolomic comparison and hepatic metabolic regulation analysis

Response to dietary L-glutamine supplementation in weaned piglets: A serum metabolomic comparison and hepatic metabolic regulation analysis1

A novel metabolomic method based on gas chromatography-mass spectrometry was applied to investigate serum metabolites in response to dietary Gln supplementation in piglets. Sixteen, 21-d-old pigs were weaned and assigned randomly to 2 isonitrogenous diets: 1) Gln diet, which contained 1% L-Gln (as-fed basis), and 2) control diet, which contained L-Ala to make this diet isonitrogenous with the Gln diet. Serum samples were collected to characterize metabolites after a 30-d treatment. in addition, 4 liver samples per treatment were collected to examine enzyme activity and gene expression involved in metabolic regulation. Results indicated that 12 metabolites were altered (P < 0.05) by Gln treatment, including carbohydrates, AA, and fatty acids. A leave-one-out cross validation of random forest analysis indicated that Pro was most important among the 12 metabolites. Thus, these data demonstrate that the control and Gln-supplemented pigs differed (P < 0.05) in terms of metabolism of carbohydrates, Pro, Tyr, and glycerophospholipids. Principal component analysis yielded separate clusters of profiles between the Gln and control groups. Metabolic enzyme activities of Ala aminotransferase and hexokinase increased by 26.8% (P = 0.026) and 26.2% (P = 0.004) in the liver of Gln-supplemented pigs vs. control, respectively, whereas pyruvate kinase (PK) activity decreased by 29.1% (P = 0.001). The gene expression of PK in the liver decreased by 66.1% (P = 0.034) by Gln treatment for 30 d. No differences were observed for the mRNA abundance of mammalian target of rapamycin and PPARγ. On the basis of these data, Gln treatment affected carbohydrate, lipid, and AA metabolism in the whole body of the early weaned piglets. These findings provide insight into specific metabolic pathways and lay the groundwork for the complex metabolic alteration in response to dietary Gln supplementation of pigs.

Response to weaning and dietary l-glutamine supplementation: metabolomic analysis in piglets by gas chromatography/mass spectrometry

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 L-glutamine (Gln) supplementation. Thirty-six 21-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 with 1% (w/w) Gln or isonitrogenous L-alanine, respectively, representing Gln group or control group. Serum samples were collected to characterize metabolites after a 7-d treatment. Results showed that twenty metabolites were down-regulated significantly (P<0.05) in control piglets compared with suckling ones. These data demonstrated that early weaning causes a wide range of metabolic changes across arginine and proline 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 α-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 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 decreased (P=0.00001) compared to the suckling piglets, and increased (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, amino acid 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.

Dietary l-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus

Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% L-glutamine or 1.22% L-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% L-glutamine or 1.22% L-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.

Dietary L-Glutamine Supplementation Reduces the Growth of the Morris Hepatoma 7777 in Exercise-Trained and Sedentary Rats , ,

Dietary glutamine supplementation and exercise have been reported independently to enhance immune function and reduce tumor growth. We study the effect of both of these interventions on the growth of the Morris Hepatoma 7777, implanted in 59 female Sprague-Dawley Buffalo rats. Rats were fed a nutritionally complete, purified diet with or without L-glutamine 20 g/kg diet and randomized to swim 3 h/d or to remain sedentary. After 14 d, the mean tumor weight of glutamine-supplemented rats was lower (P < 0.0001) than that of unsupplemented rats (5.8 ± 0.4 vs. 8.7 ± 0.5 g, respectively). Exercise did not alter tumor growth. Glutamine supplementation increased [3H] thymidine incorporation by splenocytes incubated with Concanavalin A and the proportion of natural killer cells in spleen, but not cytotoxic activity against YAC-1 cells. Glutamine supplementation did not alter glutamine concentrations in plasma (691 ± 12 μmol/L) or soleus muscle (5328 ± 102 pmol/mg) but resulted in higher (P < 0.004) plasma concentrations of leucine, isoleucine and valine, precursors of glutamine. Splenocytes from exercised rats had a higher (P < 0.001) mitogen response than those from sedentary rats. Isolated tumor cells demonstrated high rates of non-oxidative glucose and glutamine metabolism and consumption of glutamine, tryptophan and methionine. However, neither diet nor exercise significantly affected glucose or glutamine metabolism by tumor cells. The precise mechanism of tumor growth suppression by oral glutamine supplementation is not clear but may be related to changes in substrate availability, improved tumor-directed natural killer cytotoxic activity or a faster response to an immune challenge.