Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines.

Background: L-Glutamate (Glu) is a major amino acid in milk and postweaning diets for mammals (including pigs and human infants). However, effects of Glu on intestinal mucosal barrier and antioxidative functions are unknown. Objective: This study tested the hypothesis that Glu may enhance the barrier function of intestinal porcine epithelial cell line 1 (IPEC-1) cells by upregulating the expression of tight junction proteins. Methods: IPEC-1 cells were cultured with or without Glu in the presence or absence of 1 mmol/L diquat (an oxidant) for indicated time points. Cell numbers, transepithelial electrical resistance (TEER), mRNA, and protein abundance for glutamate transporter, the release of lactate dehydrogenase (LDH), and the abundance for tight junction proteins were determined. Results: Compared with 0 mmol/L Glu, 0.5-, 1-, and 2 mmol/L Glu stimulated (P < 0.05) cell growth by 13–37% at 24 h and 12–34% at 48 h, respectively. In addition, 0.5 mmol/L Glu increased (P < 0.05) TEER (by 58% at 24 h and by 98% at 48 h, respectively). These effects of Glu were associated with increased mRNA abundance for Glu transporter solute carrier family 1 member 1 (SLC1A1) by 30–130% and protein abundance for excitatory amino acid transporter 3 (encoded by SLC1A1) by 19–34%, respectively. In a cell model of oxidative stress induced by 1 mmol/L diquat, 0.5 mmol/L Glu enhanced cell viability, TEER, and membrane integrity (as indicated by the reduced release of LDH) in IPEC-1 cells by increasing the abundance of the tight junction proteins occludin, claudin-3, zonula occludens (ZO)-2, and ZO-3. Conclusion: These novel findings indicate that Glu plays an important role in mucosal barrier function by enhancing cell growth and maintaining membrane integrity in response to oxidative stress. JN utrdoi: 10.3945/jn.115.217661.

l-Glutamate Enhances Barrier and Antioxidative Functions in Intestinal Porcine Epithelial Cells

The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG) At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37 Results showed that DON significantly (P<005) induced oxidative stress in piglets, while this stress was remarkably reduced with glutamic acid supplementation according to the change of oxidative parameters in blood and tissues Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition

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Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol.

l-Glutamate (Glu) has traditionally not been considered as a nutrient needed in diets for humans and other animals (including swine) due to the unsubstantiated assumption that animals can synthesize sufficient amounts of Glu to meet their needs. The lack of knowledge about Glu nutrition has contributed to suboptimal efficiency of global livestock production. Over the past 25 years, there has been growing interest in Glu metabolism in the pig, which is an agriculturally important species and also a useful model for studying human biology. Because of analytical advances in its analysis, Glu is now known to be a highly abundant free amino acid in milk and intracellular fluid, a major constituent of food and tissue proteins, and a key regulator of gene expression, cell signaling, and anti-oxidative reactions. Emerging evidence shows that dietary supplementation with 2% Glu maintains gut health and prevents intestinal dysfunction in weanling piglets, while enhancing their growth performance and survival. In addition, the inclusion of 2% Glu is required for dietary arginine to maximize the growth performance and feed efficiency in growing pigs, whereas dietary supplementation with 2% Glu reduces the loss of skeletal muscle mass in endotoxin-challenged pigs. Furthermore, supplementing 2% Glu to a corn- and soybean-meal-based diet promotes milk production by lactating sows. Thus, an adequate amount of dietary Glu as a quantitatively major nutrient is necessary to support maximum growth, development, and production performance of swine. These results also have important implications for improving the nutrition and health of humans and other animals.

L-Glutamate nutrition and metabolism in swine.

Dietary protein digestion is an efficient process resulting in the absorption of amino acids by epithelial cells, mainly in the jejunum. Some amino acids are extensively metabolized in enterocytes supporting their high energy demand and/or production of bioactive metabolites such as glutathione or nitric oxide. In contrast, other amino acids are mainly used as building blocks for the intense protein synthesis associated with the rapid epithelium renewal and mucin production. Several amino acids have been shown to support the intestinal barrier function and the intestinal endocrine function. In addition, amino acids are metabolized by the gut microbiota that use them for their own protein synthesis and in catabolic pathways releasing in the intestinal lumen numerous metabolites such as ammonia, hydrogen sulfide, branched-chain amino acids, polyamines, phenolic and indolic compounds. Some of them (e.g. hydrogen sulfide) disrupts epithelial energy metabolism and may participate in mucosal inflammation when present in excess, while others (e.g. indole derivatives) prevent gut barrier dysfunction or regulate enteroendocrine functions. Lastly, some recent data suggest that dietary amino acids might regulate the composition of the gut microbiota, but the relevance for the intestinal health remains to be determined. In summary, amino acid utilization by epithelial cells or by intestinal bacteria appears to play a pivotal regulator role for intestinal homeostasis. Thus, adequate dietary supply of amino acids represents a key determinant of gut health and functions.

Amino Acids in Intestinal Physiology and Health.

The aim of the present work was to examine in pigs the effect of a dietary supplementation with the flavor enhancer monosodium glutamate (MSG) on intestinal amino acid metabolism. For this purpose, pi

Portal hyperglutamatemia after dietary supplementation with monosodium glutamate in pigs.

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Portal hyperglutamatemia after dietary supplementation with monosodium glutamate in pigs.