Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability

Ghouzali, Ibtissem; Lemaître, Caroline; Bahlouli, W.; Azhar, S.; Bôle‐Feysot, Christine; Méleine, Mathieu; Ducrotté, Philippe; Déchelotte, Pierre; Coëffier, Moı̈se

doi:10.1016/j.bbagen.2016.08.010

Cited by 13 publications

(28 citation statements)

References 52 publications

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“…At day 11, ABA mice were randomized and divided into two sub-groups with or without supplementation. Gln was distributed in water at the dose of 2 g/kg/day, as previously described [35]. Like Gln, BCAA were diluted in water, but consisted of a combination of three amino acids with a ratio of 2:1:1 (Leu, Ile, Val) to reach 25 g/L (2.5%) [36].…”

Section: Methodsmentioning

confidence: 99%

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Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

et al. 2019

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Background: During activity-based anorexia (ABA) in mice, enhanced paracellular permeability and reduced protein synthesis have been shown in the colon while the gut–brain axis has received increasing attention in the regulation of intestinal and mood disorders that frequently occur during anorexia nervosa, a severe eating disorder for which there is no specific treatment. In the present study, we assessed the effects of oral glutamine (Gln) or branched-chain amino acids (BCAA) supplementation during ABA to target intestinal functions, body composition and feeding behavior. Methods: C57BL/6 male mice were randomized in Control (CTRL) and ABA groups. After ABA induction, mice received, or not, either 1% Gln or 2.5% BCAA (Leu, Ile, Val) for one week in drinking water. Results: Neither Gln nor BCAA supplementation affected body weight and body composition, while only Gln supplementation slightly increased food intake. ABA mice exhibited increased paracellular permeability and reduced protein synthesis in the colonic mucosa. Oral Gln restored colonic paracellular permeability and protein synthesis and increased the mucin-2 mRNA level, whereas BCAA did not affect colonic parameters. Conclusion: In conclusion, oral Gln specifically improves colonic response during ABA. These data should be further confirmed in AN patients.

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Section: Methodsmentioning

confidence: 99%

“…Colonic paracellular permeability was assessed by measuring fluxes of FITC-Dextran (4 kDa) in Ussing chambers (Harvard Apparatus, Holliston, MA, USA), as previously described [35]. Briefly, a physiological solution (HBSS) was placed in mucosal and serosal sides.…”

Section: Methodsmentioning

confidence: 99%

Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

et al. 2019

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“…49,50,54 We have recently demonstrated that glutamine supplementation prevented colonic hyperpermeability and reduced proinflammatory cytokine production in WAS mice. 21 Zhou et al have recently reported that reduced expression of glutamine synthase in colon tissues of IBS-D patients may lead to decreased claudin-1 expression, and consequently increased intestinal permeability. 55 In the same way, we have shown ex vivo that glutamine supplementation increased claudin-1 expression in the colonic mucosa of IBS-D patients.…”

Section: Discussionmentioning

confidence: 99%

“…21,[23][24][25] After one week of acclimatization at 23°C (12-hour light-dark cycle; dark phase: 8:00 PM -8:00 AM), WAS model was performed during 1 hour per day during 10 consecutive days as previously described. 21 After the last WAS procedure, mice were euthanized. Colonic samples were either taken, washed with ice-cold PBS and immediately frozen until further analysis or immediately used to evaluate paracellular permeability.…”

Section: Water Avoidance Stressmentioning

confidence: 99%

“…In this latter study, both pharmacological immunoproteasome inhibition and β2i subunit deficiency limited colonic hyperpermeability and improved occludin expression. 21 To better understand the underlying mechanisms, we thus aimed (i) to evaluate the colonic proteome in wild-type and β2i immunoproteasome subunit knock-out (β2i -/-) mice during water avoidance stress (WAS) and (ii) to investigate the colonic expression of 49 ubiquitinated proteins in IBS-D patients.…”

Section: Introductionmentioning

confidence: 99%

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Colonic Proteome Signature in Immunoproteasome-Deficient Stressed Mice and Its Relevance for Irritable Bowel Syndrome

et al. 2018

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A role for immunoproteasome in the regulation of intestinal permeability has been previously suggested both in mice during water avoidance stress (WAS) and in patients with irritable bowel syndrome (IBS). Here, we provide evidence that the ubiquitin-proteasome system (UPS) contributes to the pathophysiology of IBS. Indeed, we report that colonic proteome is altered in WAS mice and that β2i subunit deficiency modifies the proteome response that is associated with a limitation of colonic hyperpermeability. Interestingly, we show specific alterations of proteins involved in UPS, mitochondrial and energy metabolism. We also report changes in the pattern of colonic ubiquitome in diarrhea-predominant IBS patients (IBS-D), and particularly a reduced expression of ubiquitinated proteins involved in the NF-κB inflammatory signaling pathway. All these data suggest that immunoproteasome targeting may represent a new therapeutic strategy for the treatment of IBS patients with increased intestinal permeability.

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Gut microbiota depletion affects nutritional and behavioral responses to activity-based anorexia model in a sex-dependent manner

et al. 2021

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Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability

Cited by 13 publications

References 52 publications

Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia

Colonic Proteome Signature in Immunoproteasome-Deficient Stressed Mice and Its Relevance for Irritable Bowel Syndrome

Gut microbiota depletion affects nutritional and behavioral responses to activity-based anorexia model in a sex-dependent manner

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