BioMetals

, Volume 31, Issue 2, pp 217–232 | Cite as

Effect of zinc intake on hepatic autophagy during acute alcohol intoxication

  • Juan P. Liuzzi
  • Vijaya Narayanan
  • Huong Doan
  • Changwon Yoo
Article

Abstract

Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol. A mouse model of binge ethanol feeding was utilized to analyze the effect of low, adequate, and high zinc intake on hepatic autophagic flux during ethanol intoxication. Autophagic flux was inferred by analyzing LC3II/LC3I ratio, protein levels of p62/SQSTM1, Beclin1 and Atg7, and phosphorylation of 4EBP1. In addition, the degradation of the fusion protein LC3-GFP and the formation of autophagosomes and autolysosomes were evaluated in cells. Ethanol treatment stimulated autophagy in mice and cells. High zinc intake resulted in enhanced autophagy in mice exposed to ethanol. Conversely, zinc deficiency was consistently associated with impaired ethanol-induced autophagy in mice and cells. Zinc-deficient mice exhibited a high degree of ethanol-driven steatosis. Furthermore, zinc depletion increased apoptosis in cells exposed to ethanol. The results of this study suggest that adequate zinc intake is necessary for proper stimulation of autophagy by ethanol. Poor zinc status is commonly found among alcoholics and could likely contribute to faulty autophagy.

Keywords

Autophagy Zinc Ethanol Liver Zinc intake Mice 

Notes

Acknowledgements

This study was supported by NIH 1R03AA022451-01.

Supplementary material

10534_2018_77_MOESM1_ESM.doc (84 kb)
Supplementary material 1 (DOC 84 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Dietetics and Nutrition, Robert Stempel College of Public Health and Social WorkFlorida International UniversityMiamiUSA
  2. 2.Department of Biostatistics, Robert Stempel College of Public Health and Social WorkFlorida International UniversityMiamiUSA

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