Oral supplementation of choline attenuates the development of alcohol-related liver disease (ALD) – PubMed Black Hawk Supplements

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

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

Victor Sánchez et al. Mol Med. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1

Effect of supplementing choline on markers of liver damage in EtOH-fed female C57BL/6 J mice. Representative pictures of (A) hematoxylin & eosin (H&E, magnification 200 × and 400 x) and Oil-Red O staining in liver tissue (magnification 630 x), 4-hydroxynonenal (4-HNE) protein adduct staining (magnification 200 x), (B) scoring of liver sections, number of (C) neutrophil granulocytes and (D) Ly6G-positive cells per microscopic field, (E) interleukin 6 (IL-6) protein concentration, (F) nitric oxide (NOx) concentration in liver tissue as well as (G) densitometric analysis of 4-HNE protein adducts. Data are presented as box and whisker plots, n = 8/group except for (G) n = 6–8/group. ap < 0.05 compared with mice fed the C diet, cp < 0.05 compared with mice fed the C + Choline diet, and dp < 0.05 compared with mice fed the EtOH + Choline diet. C control Lieber DeCarli diet, EtOH ethanol-enriched Lieber DeCarli diet, Ly6G lymphocyte antigen 6 complex locus G6D

Fig. 2
Fig. 2

Effect of supplementing choline on markers of intestinal permeability in EtOH-fed female C57BL/6 J mice. (A) Xylose permeation assessed in small intestinal everted tissue sacs, (B) plasma bacterial endotoxin levels, (C) representative pictures (magnification 630 x) and (D) densitometric analysis of zonula occludens-1 (ZO-1) protein as well as (E) nitric oxide (NOx) concentration in small intestinal tissue. Data are presented as box and whisker plots, n = 7–8/group. ap < 0.05 compared with mice fed the C diet. cp < 0.05 compared with mice fed the C + Choline diet, and dp < 0.05 compared with mice fed the EtOH + Choline diet. C control Lieber DeCarli diet, EtOH ethanol-enriched Lieber DeCarli diet

Fig. 3
Fig. 3

Effect of supplementing choline on microbiota composition in small intestine in EtOH-fed female C57BL/6 J mice. (A) PCoA plots based on robust Aitchison distances (RPCA), (B) alpha diversity based on Shannon entropy and Faith´s phylogenetic indices, (C) relative abundances of bacterial genera (for sequences that were not annoted to the genus level last available level is shown) as well as (D) Venn diagram of group core features at genus level. Indices were shown as box plots, n = 8/group. C control Lieber DeCarli diet, EtOH ethanol-enriched Lieber DeCarli diet

Fig. 4
Fig. 4

Effect of choline on EtOH-induced intestinal barrier dysfunction in small intestinal everted tissue sacs. (A) Schematic drawing of experimental set-up, xylose permeation of everted gut sacs (B) treated with EtOH and choline and (C) treated with EtOH, choline and choline oxidase inhibitor (dimbunol) as well as (D) nitrite (NOx) concentration in everted gut sacs treated with EtOH, choline and dimbunol. Data are presented as box and whisker plots, for (B) n = 5–6/group, (C) n = 6–7/group and (D) n = 6/group. ap < 0.05 compared with control everted gut sacs, cp < 0.05 compared with EtOH + Choline treated everted gut sacs. (A) was created with BioRender.com

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