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Effects of binge ethanol on lipid homeostasis and oxidative stress in a rat model of nonalcoholic fatty liver disease

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Abstract

Excess fat accumulation renders the liver more vulnerable to ethanol, but it is still unclear how alcohol enhances lipid dysmetabolism and oxidative stress in a pre-existing steatosis condition. The effects produced by binge ethanol consumption in the liver of male Wistar rats fed a standard (Ctrl) or a high-fat diet HFD were compared. The liver status was checked through tissue histology and standard serum parameters. Alteration of hepatic lipid homeostasis and consequent oxidative unbalance were assessed by quantifying the mRNA expression of the lipid-regulated peroxisome proliferator-activated receptors (PPARs), of the cytochromes CYP2E1 and CYP4A1, and of some antioxidant molecules such as the metallothionein isoforms MT1 and MT2 and the enzymes catalase and superoxide dismutase. The number of adipose differentiation-related protein (ADRP)-positive lipid droplets (LDs) was evaluated by immunohistochemical staining. As a response to the double insult of diet and ethanol the rat liver showed: (1) a larger increase in fat accumulation within ADRP-positive LDs; (2) stimulation of lipid oxidation in the attempt to limit excess fat accumulation; (3) induction of antioxidant proteins (MT2, in particular) to protect the liver from the ethanol-induced overproduction of oxygen radicals. The data indicate an increased susceptibility of fatty liver to ethanol and suggest that the synergistic effect of diet and ethanol on lipid dysmetabolism might be mediated, at least in part, by PPARs and cytochromes CYP4A1 and CYP2E1.

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Acknowledgments

This work was supported by research grants from Compagnia San Paolo Torino (prat. no. 2009.1824-1067/IT/pv) and MIUR-COFIN 2008 (prot. 20089SRS2X_002). We thank Monica Schweier and Giulia Vecchione for their generous experimental activity and Mr. V. Capicchioni for his helpful technical assistance. A special thanks to Dr Giorgio Filosa for his help with serum values assessment and to Prof. Emilia Fugassa for her critical reading of the manuscript and for the constant support and encouragement.

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Authors and Affiliations

  1. Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, 16132, Genoa, Italy

    Elena Grasselli, Adriana Voci, Ilaria Demori, Andrea D. Compalati, Gabriella Gallo & Laura Vergani

  2. Dipartimento di Scienze Biomolecolari, Università di Urbino, via I Maggetti 26, 61029, Urbino, Italy

    Rita De Matteis

  3. Istituto Nazionale Biostrutture e Biosistemi (INBB), Rome, Italy

    Elena Grasselli & Laura Vergani

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  1. Elena Grasselli
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  2. Adriana Voci
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  3. Ilaria Demori
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Correspondence to Laura Vergani.

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Grasselli, E., Voci, A., Demori, I. et al. Effects of binge ethanol on lipid homeostasis and oxidative stress in a rat model of nonalcoholic fatty liver disease. J Physiol Biochem 70, 341–353 (2014). https://doi.org/10.1007/s13105-013-0308-x

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  • DOI: https://doi.org/10.1007/s13105-013-0308-x

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