Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Met...

Full description

Saved in:
Bibliographic Details
Main Authors: Kusum K. Kharbanda, Sandra L. Todero, Adrienne L. King, Natalia A. Osna, Benita L. McVicker, Dean J. Tuma, James L. Wisecarver, Shannon M. Bailey
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2012/962183
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832549379431464960
author Kusum K. Kharbanda
Sandra L. Todero
Adrienne L. King
Natalia A. Osna
Benita L. McVicker
Dean J. Tuma
James L. Wisecarver
Shannon M. Bailey
author_facet Kusum K. Kharbanda
Sandra L. Todero
Adrienne L. King
Natalia A. Osna
Benita L. McVicker
Dean J. Tuma
James L. Wisecarver
Shannon M. Bailey
author_sort Kusum K. Kharbanda
collection DOAJ
description Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection.
format Article
id doaj-art-6743cadb2f644066b57fbf4fe06b511a
institution Kabale University
issn 2090-3448
2090-3456
language English
publishDate 2012-01-01
publisher Wiley
record_format Article
series International Journal of Hepatology
spelling doaj-art-6743cadb2f644066b57fbf4fe06b511a2025-02-03T06:11:27ZengWileyInternational Journal of Hepatology2090-34482090-34562012-01-01201210.1155/2012/962183962183Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain ProteomeKusum K. Kharbanda0Sandra L. Todero1Adrienne L. King2Natalia A. Osna3Benita L. McVicker4Dean J. Tuma5James L. Wisecarver6Shannon M. Bailey7Research Service-151, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE 68105, USAResearch Service-151, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE 68105, USADepartment of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USAIntroduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection.http://dx.doi.org/10.1155/2012/962183
spellingShingle Kusum K. Kharbanda
Sandra L. Todero
Adrienne L. King
Natalia A. Osna
Benita L. McVicker
Dean J. Tuma
James L. Wisecarver
Shannon M. Bailey
Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
International Journal of Hepatology
title Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
title_full Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
title_fullStr Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
title_full_unstemmed Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
title_short Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome
title_sort betaine treatment attenuates chronic ethanol induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome
url http://dx.doi.org/10.1155/2012/962183
work_keys_str_mv AT kusumkkharbanda betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT sandraltodero betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT adriennelking betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT nataliaaosna betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT benitalmcvicker betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT deanjtuma betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT jameslwisecarver betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome
AT shannonmbailey betainetreatmentattenuateschronicethanolinducedhepaticsteatosisandalterationstothemitochondrialrespiratorychainproteome