Oral supplementation of choline attenuates the development of alcohol-related liver disease (ALD)

Mol Med. 2024 Oct 18;30(1):181. doi: 10.1186/s10020-024-00950-4.

Abstract

Background: Chronic alcohol intake is associated with alterations of choline metabolism in various tissues. Here, we assessed if an oral choline supplementation attenuated the development of alcohol-related liver disease (ALD) in mice.

Methods: Female C57BL/6 J mice (n = 8/group) were either pair-fed a liquid control diet, or a Lieber DeCarli liquid diet (5% ethanol) ± 2.7 g choline/kg diet for 29 days. Liver damage, markers of intestinal permeability and intestinal microbiota composition were determined. Moreover, the effects of choline on ethanol-induced intestinal permeability were assessed in an ex vivo model.

Results: ALD development as determined by liver histology and assessing markers of inflammation (e.g., nitric oxide, interleukin 6 and 4-hydroxynonenal protein adducts) was attenuated by the supplementation of choline. Intestinal permeability in small intestine being significantly higher in ethanol-fed mice was at the level of controls in ethanol-fed mice receiving choline. In contrast, no effects of the choline supplementation were found on intestinal microbiota composition. Choline also significantly attenuated the ethanol-induced intestinal barrier dysfunction in small intestinal tissue ex vivo, an effect almost entirely abolished by the choline oxidase inhibitor dimbunol.

Conclusion: Our results suggest that an oral choline supplementation attenuates the development of ALD in mice and is related to a protection from intestinal barrier dysfunction.

Keywords: Choline oxidase; Ethanol; Intestinal barrier; Lieber DeCarli diet; Nitrite.

MeSH terms

  • Administration, Oral
  • Animals
  • Choline* / administration & dosage
  • Choline* / metabolism
  • Dietary Supplements*
  • Disease Models, Animal
  • Ethanol / adverse effects
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic* / drug therapy
  • Liver Diseases, Alcoholic* / etiology
  • Liver Diseases, Alcoholic* / metabolism
  • Liver Diseases, Alcoholic* / pathology
  • Liver Diseases, Alcoholic* / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Permeability

Substances

  • Choline
  • Ethanol