The high metabolic cost of a functional gut

Schoor, Sophie R D van der; Reeds, Peter J.; Stoll, Barbara J.; Henry, Joe F.; Rosenberger, J; Burrin, Douglas G.; Goudoever, Johannes B. van

doi:10.1053/gast.2002.37062

Cited by 103 publications

(85 citation statements)

References 19 publications

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“…We argue against this possibility, because the ligand-binding results did not show any direct interactions between Lys and 5-HT 3 receptors, and Lys did not affect the normal defecation pattern. Second, because secretory glycoprotein synthesis, rather than the catabolism (38)(39)(40), appears to be a major metabolic fate of nutritionally indispensable amino acids, it is possible that the protective effect of Lys was mediated by an increased rate of glycoprotein synthesis within the intestines. The intestinal mucosa is structurally protected by glycoproteins (mucins) (41), but the content and role of Lys in the core proteins of the intestinal mucins is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The intestinal mucosa is structurally protected by glycoproteins (mucins) (41), but the content and role of Lys in the core proteins of the intestinal mucins is unclear. Third, microbial synthesis of Lys was shown in the gastrointestinal tract (38). This Lys is made available through protein breakdown and its intestinal uptake, and it is possible that the high dietary Lys load blocked this protein breakdown in an unspecified way.…”

Section: Discussionmentioning

confidence: 99%

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l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Smriga

Torii

2003

Proc. Natl. Acad. Sci. U.S.A.

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S tress and stress-induced anxiety play a major role in functional intestinal disorders (1). The stimulation of intestinal contraction and colonic transit are the most consistent patterns in the motility response of the intestinal tract to acute stress (2, 3); however, the stress-gut interactions are enormously complex (1). Both stress-induced anxiety and intestinal disorders are traced, from among other molecular pathologies, to the inappropriate responses of the central and͞or peripheral serotonin (5-HT) system (4, 5). Among the 5-HT receptors, the 5-HT 4 receptor plays a ''prostress'' role in the gut and throughout the body by mobilizing energy and facilitating behavioral, gastrointestinal, and cardiovascular stress responses (6, 7).5-HT 4 receptors are located within the cells and neurons of the gastrointestinal tract (6,8). Agonists on the 5-HT 4 receptor increase cholinergic transmission (9) and thus contract the smooth muscle in the rat and guinea pig ileum † and the human colon (11). Antagonists on the 5-HT 4 receptor do not affect normal, healthy gut function (12) but prevent the disturbances caused by stress (4) or high 5-HT activity (13). Thus, 5-HT 4 receptor antagonists are promising targets for the treatment of diarrhea-predominant irritable bowel syndrome (12). In addition to their effect on the gastrointestinal tract, 5-HT 4 antagonists block corticosteroid secretion in the adrenal cortex (14), 5-HTinduced tachycardia (15, 16), and stress-induced anxiety (17).However, the 5-HT receptor system is heterogeneous (18), and direct receptor targeting often causes side effects, such as diarrhea, gastric bleeding, and anxiety (19). Therefore, it is not surprising that few satisfying pharmacological treatments of stress-triggered, 5-HT-mediated intestinal disorders exist and that other therapeutic approaches, namely nutritional ones, are sought (20)(21)(22)). An interesting candidate to include in ''nutritional management'' of stress-related gastrointestinal disorders would be an essential amino acid, L-lysine (Lys). Lys blunted stress-induced anxiety in rats (23), whereas a dietary deficiency of Lys increased stress-induced colonic transit and anxiety, because of an enhanced transmission of 5-HT in the amygdala (24).Because the effects of Lys overlap with the ''antistress'' effects of the 5-HT 4 receptor antagonists (4), we hypothesized that dietary Lys could act as a partial antagonist on the 5-HT 4 receptors. The present study examined whether the provision of oral L-lysine might result in the blockage of 5-HT-mediated pathologies linked to stress exposure and͞or 5-HT sensitization in rats. Ileum contractions, stress-induced fecal excretion, diarrhea, anxiety, and tachycardia were monitored. The fractions obtained were washed once by centrifugation with 10-fold volume of the buffer, and the microsomal fraction was stored as receptor at Ϫ80°C until use. To determine the binding degree, the inhibition rate of Lys and a positive reference substance were calculated from binding of a tracer to a receptor. D...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Smriga

Torii

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Intestinal epithelial cell proliferation, differentiation, and apoptosis play important roles in intestinal development, maintenance, and recovery from tissue damage (44). In addition, epithelial cells in the pig intestine have notably high energy demands due to the rapid renewal of the epithelium (within few days) (2,36). Previous studies showed the activities of key metabolic enzymes in enterocytes changed during the suckling-weaning transition in pigs (20,21).…”

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confidence: 99%

Differential expression of proteins involved in energy production along the crypt-villus axis in early-weaning pig small intestine

Xiong

Yang

Tan

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Weaning of piglets reflects intestinal dysfunction and atrophy and affected the physiological state of enterocytes. However, few studies have defined physiological state of enterocytes along the crypt-villus axis in early-weaning piglets. A total of 16 piglets from 8 litters were used in the experiment. One group of piglets was nursed by sows until age 21 days, and another group was weaned at age 14 days and then fed creep feed instead of breast milk for 7 days. Piglets were killed at 21 days, and the jejunum segments were dissected. After sequential isolation of jejunum epithelial cells along the crypt-villus axis, their proteins were analyzed through the isobaric tags for relative and absolute quantification, and proteins involved in the mammalian target of rapamycin signaling pathway and proliferating cell nuclear antigen abundances in jejunal epithelial cells of weaning or suckling group were determined by Western blotting. The differential proteins in three cell fractions were identified and analyzed. The results showed that proteins involved in the tricarboxylic acid cycle, ␤-oxidation, and the glycolysis pathway were significantly downregulated in the upper and middle villus of the early-weaned group. However, proteins involved in glycolysis were significantly upregulated in crypt cells. In addition, Western blot analysis showed that the expression of mammalian target of rapamycin pathway-related proteins was decreased (P ＜ 0.05) in the earlyweaned group. The present results showed that early-weaning differentially affect the expression of proteins involved in energy production of enterocytes along the jejunal crypt-villus axis.weaning; enterocyte; crypt-villus axis; piglet EARLY WEANING (14-to 21-day weaning age) of piglets is stressful and is characterized by poor growth, decreased feed intake, and diarrhea, because they are abruptly forced to combined stressors, including maternal and littermate separations, changes in diet, and establishment of a new social hierarchy (30, 31). Early weaning stress results in increased intestinal dysfunction and atrophy, impaired mucosal barrier function, and an imbalance of intestinal microbiota (13, 30). Inadequate food intake immediately after weaning and insufficient energy intake may contribute to the changes in intestinal morphology (25,35).The intestinal epithelium is characterized by rapidly proliferating cells organized into structures called crypts, which invaginate into the underlying mesenchyme, and villi, which project into the lumen (6). Furthermore, epithelial cells undergo functional and morphological differentiation during migration along the crypt-villus axis from the crypt to the tip of the villus (22, 43). Intestinal epithelial cell proliferation, differentiation, and apoptosis play important roles in intestinal development, maintenance, and recovery from tissue damage (44). In addition, epithelial cells in the pig intestine have notably high energy demands due to the rapid renewal of the epithelium (within few days) (2, 36). Previous studies showed...

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“…In particular, this inclusion is necessary because the "extraction" of amino acids by the gut is not irreversible, as is often assumed for a short infusion period. In fact, van der Schoor et al (28) have recently showed that almost 50% of the lysine in the portal vein is derived from recycling of glycoproteins by the gut within a 6-h period; so orally delivered isotope is "extracted" by the gut, incorporated into proteins to be secreted into the lumen, and then degraded such that the extracted amino acids eventually enter the systemic circulation and central plasma pool. Therefore, subtracting this extraction from the infusion dose is not appropriate, given that this isotope is eventually reintroduced into the plasma pool.…”

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confidence: 99%

Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet

Wilkinson¹,

Bertolo²,

Brunton³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Arginine is conditionally indispensable in the neonate, and its synthesis in the intestine is not sufficient to meet requirements. It is not known how neonatal endogenous arginine synthesis is regulated and the degree to which proline and glutamate are used as precursors. Primed, constant intraportal and intragastric infusions of L-[U-14 C]proline and L- [3,4-3 H]glutamate, and intragastric L-[guanido-14 C]arginine were used to measure whole body and first-pass intestinal arginine synthesis in 10 neonatal piglets fed generous (1.80) quantities of arginine for 5 days. Glutamate tracer was not detected in arginine, indicating a biologically insignificant conversion of Ͻ1% of arginine flux. Endogenous arginine synthesis from proline had obligatory (0.36 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) and maximal (0.68 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) levels (P Ͻ 0.05, pooled SE 0.05). Although first-pass gut metabolism is responsible for 42-63% of whole body arginine synthesis, the gut is incapable of upregulating proline to arginine conversion during arginine deficiency, compared with a more than threefold increase without firstpass gut metabolism. These data suggest that upregulation of prolineto-arginine conversion occurs via increased arterial extraction of proline by the gut or in nonintestinal tissues. This study demonstrates that dietary arginine is an important regulator of endogenous arginine synthesis in the neonatal piglet and that proline, but not glutamate, is an important precursor for arginine synthesis in the neonate.

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The high metabolic cost of a functional gut

Cited by 103 publications

References 19 publications

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

l -Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats

Differential expression of proteins involved in energy production along the crypt-villus axis in early-weaning pig small intestine

Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet

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