Research article summary (published 29 Sep 2009):

Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha.

Full Abstract

Alcoholic steatosis is a fundamental metabolic disorder in the progression of alcoholic liver disease. Zinc deficiency is one of the most consistently observed biochemical/nutritional manifestations of alcoholic liver disease. The purpose of this study is to determine whether dietary zinc supplementation to mice previously exposed to alcohol could reverse alcoholic steatosis. Male 129S mice were pair-fed an alcohol or isocaloric maltose dextrin liquid diet for 16 weeks with or without dietary zinc supplementation for the last 4 weeks. Zinc supplementation significantly attenuated alcohol-mediated increases in hepatic triglyceride, cholesterol, and free fatty acids in association with accelerated hepatic fatty acid oxidation and very low density lipoproteins (VLDL) secretion. Hepatic genes related to fatty acid oxidation and VLDL secretion were up-regulated by zinc supplementation, which was accompanied by restoring activity of hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferators activated receptor-alpha (PPAR-alpha). Zinc supplementation enhanced alcohol metabolism and attenuated oxidative stress and liver injury. Zinc supplementation also normalized alcohol-mediated increases in plasma triglycerides and partially reversed decrease in gonadal adipose depot mass. Studies in HepG2 cells showed that zinc deprivation significantly suppressed the DNA-binding activities of HNF-4alpha and PPAR-alpha, and reduced HNF-4alpha and PPAR-alpha target proteins. Consequently, zinc deprivation caused cellular accumulation of lipid droplets, triglycerides and free fatty acids in the HepG2 cells. CONCLUSION: Zinc supplementation reverses alcoholic steatosis, and reactivation of HNF-4alpha and PPAR-alpha by increasing zinc availability and inhibiting oxidative stress are potential mechanisms underlying these beneficial effects of zinc on hepatic lipid homeostasis.

Author information

Author/s: Kang, Xinqin (X); Zhong, Wei (W); Liu, Jie (J); Song, Zhenyuan (Z); McClain, Craig J (CJ); Kang, Y James (YJ); Zhou, Zhanxiang (Z);

Affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.

Grants: R01 AA014623-01A2 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Hepatology (Baltimore, Md.) (Hepatology), published in United States. (Language: eng)

Reference: 2009-Oct; vol 50 (issue 4) : pp 1241-50

Dates: Created 2009/10/05; Completed 2009/10/20; Revised 2009/11/09;

PMID: 19637192, status: MEDLINE (last retrieval date: 11/10/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alanine Transaminase - metabolism Animals Body Weight - drug effects Cell Line, Tumor Cholesterol - metabolism Dietary Supplements Disease Models, Animal Fatty Acids, Nonesterified - metabolism Fatty Liver, Alcoholic - metabolism; prevention & control Hepatocyte Nuclear Factor 4 - metabolism

Homeostasis - drug effects; physiology Liver - drug effects; metabolism; pathology Male Mice Mice, Inbred Strains Organ Size - drug effects Oxidative Stress - drug effects; physiology PPAR alpha - metabolism Triglycerides - metabolism Zinc - administration & dosage; metabolism; pharmacology

Associated Chemicals: Fatty Acids, Nonesterified (0) ; Hepatocyte Nuclear Factor 4 (0) ; Hnf4a protein, mouse (0) ; PPAR alpha (0) ; Triglycerides (0) ; Cholesterol (57-88-5) ; Zinc (7440-66-6) ; Alanine Transaminase (EC 2.6.1.2)

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