Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice

J Nutr Biochem. 2016 Jan;27:16-26. doi: 10.1016/j.jnutbio.2015.08.012. Epub 2015 Aug 20.

Abstract

Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury.

Keywords: Adherens junction; Alcohol; Cadherin; Claudin; Occludin; Oxidative stress; Tight junction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adherens Junctions / drug effects*
  • Animals
  • Body Weight / drug effects
  • Colon / drug effects*
  • Colon / physiopathology
  • Ethanol / toxicity*
  • Fatty Liver / physiopathology*
  • Female
  • Glutamine / administration & dosage*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / physiopathology
  • Mice
  • Mice, Inbred C57BL

Substances

  • Glutamine
  • Ethanol