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Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

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Abstract

Purpose

Several clinical studies suggested that light-to-moderate alcohol intake could alleviate nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism is still poorly understood.

Methods

Mice fed a high-fat diet (HFD) were submitted or not to moderate ethanol intake for 3 months (ca. 10 g/kg/day) via drinking water. Biochemical, analytical and transcriptomic analyses were performed in serum and liver.

Results

Serum ethanol concentrations in ethanol-treated HFD mice comprised between 0.5 and 0.7 g/l throughout the experiment. NAFLD improvement was observed in ethanol-treated HFD mice as assessed by reduced serum transaminase activity. This was associated with less microvesicular and more macrovacuolar steatosis, the absence of apoptotic hepatocytes and a trend towards less fibrosis. Liver lipid analysis showed increased amounts of fatty acids incorporated in triglycerides and phospholipids, reduced proportion of palmitic acid in total lipids and higher desaturation index, thus suggesting enhanced stearoyl-coenzyme A desaturase activity. mRNA expression of several glycolytic and lipogenic enzymes was upregulated. Genome-wide expression profiling and gene set enrichment analysis revealed an overall downregulation of the expression of genes involved in collagen fibril organization and leukocyte chemotaxis and an overall upregulation of the expression of genes involved in oxidative phosphorylation and mitochondrial respiratory chain complex assembly. In addition, mRNA expression of several proteasome subunits was upregulated in ethanol-treated HFD mice.

Conclusions

Moderate chronic ethanol consumption may alleviate NAFLD by several mechanisms including the generation of non-toxic lipid species, reduced expression of profibrotic and proinflammatory genes, restoration of mitochondrial function and possible stimulation of proteasome activity.

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Acknowledgements

This work was supported by a grant from the Agence Nationale de la Recherche (ANR STEATOX project ANR-13-CESA-0009). Simon Bucher was a recipient of a joint fellowship from the Région Bretagne (ARED) and ANR. We are grateful to Alain Fautrel and Marine Seffals (histopathology platform H2P2), Laurence Bernard-Touami (animal care facility ARCHE), Stéphanie Dutertre (microscopy Rennes imaging center platform MRIC), all from the SFR Biosit UMS CNRS 3480-INSERM 018 SFR, for their excellent technical support. We also wish to thank Nicolas Collet (Laboratoire de Biochimie-Toxicologie, CHU de Rennes) for his skilled technical assistance for the serum analyses. We are grateful to INSERM (Institut National de la Recherche et de la Santé Médicale) for its constant financial support.

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Authors and Affiliations

  1. Univ Rennes, Inserm, Inra, Institut NUMECAN (Nutrition Metabolisms and Cancer)-UMR_S 1241, UMR_A 1341, 35000, Rennes, France

    Simon Bucher, Karima Begriche, Cédric Coulouarn, Grégory Pinon & Bernard Fromenty

  2. Laboratoire de Biochimie-Nutrition Humaine, Agrocampus Ouest, Rennes, France

    Daniel Catheline & Vincent Rioux

  3. Pathology Department, Saint-Joseph University, Beirut, Lebanon

    Viviane Trak-Smayra

  4. Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France

    François Tiaho & Dominique Lagadic-Gossmann

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  1. Simon Bucher
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Correspondence to Bernard Fromenty.

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Bucher, S., Begriche, K., Catheline, D. et al. Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids. Eur J Nutr 59, 1619–1632 (2020). https://doi.org/10.1007/s00394-019-02017-1

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  • DOI: https://doi.org/10.1007/s00394-019-02017-1

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