Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Sudheer K Mantena; Adrienne L King; Kelly K Andringa; Heather B Eccleston; Shannon M Bailey

doi:10.1016/j.freeradbiomed.2007.12.029

Back

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Journal article

Peer reviewed

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Sudheer K Mantena, Adrienne L King, Kelly K Andringa, Heather B Eccleston and Shannon M Bailey

Free radical biology & medicine, Vol.44(7), pp.1259-1272

04/01/2008

DOI: 10.1016/j.freeradbiomed.2007.12.029

PMCID: PMC2323912

PMID: 18242193

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/2323912View

Open Access

Abstract

Fatty liver disease associated with chronic alcohol consumption or obesity/type 2 diabetes has emerged as a serious public health problem. Steatosis, accumulation of triglyceride in hepatocytes, is now recognized as a critical "first-hit" in the pathogenesis of liver disease. It is proposed that steatosis "primes" the liver to progress to more severe liver pathologies when individuals are exposed to subsequent metabolic and/or environmental stressors or "second-hits." Genetic risk factors can also influence the susceptibility to and severity of fatty liver disease. Furthermore, oxidative stress, disrupted nitric oxide (NO) signaling, and mitochondrial dysfunction are proposed to be key molecular events that accelerate or worsen steatosis and initiate progression to steatohepatitis and fibrosis. This review article will discuss the following topics regarding the pathobiology and molecular mechanisms responsible for fatty liver disease: (1) the "two-hit" or "multi-hit" hypothesis, (2) the role of mitochondrial bioenergetic defects and oxidant stress, (3) the interplay between NO and mitochondria in fatty liver disease, (4) genetic risk factors and oxidative stress-responsive genes, and (5) the feasibility of antioxidants for treatment.

Alcohols - pharmacology

Animals

Antioxidants - pharmacology

Disease Progression

Fatty Acids - metabolism

Fatty Liver - chemically induced

Fatty Liver - etiology

Fibrosis - pathology

Free Radicals

Hepatocytes - cytology

Humans

Mitochondria - pathology

Models, Biological

Obesity

Oxidative Stress

Proteomics - methods

Details

Title: Subtitle: Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases
Creators: Sudheer K Mantena - University of Alabama at Birmingham
Adrienne L King - University of Alabama at Birmingham
Kelly K Andringa - University of Alabama at Birmingham
Heather B Eccleston - University of Alabama at Birmingham
Shannon M Bailey - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.44(7), pp.1259-1272
DOI: 10.1016/j.freeradbiomed.2007.12.029
PMID: 18242193
PMCID: PMC2323912
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Grant note: R21 DK073775-02 / NIDDK NIH HHS R01 AA015172-04 / NIAAA NIH HHS DK73775 / NIDDK NIH HHS AA15172 / NIAAA NIH HHS R01 AA015172 / NIAAA NIH HHS R21 DK073775 / NIDDK NIH HHS
Language: English
Date published: 04/01/2008
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9984548670602771

Metrics

13 Record Views

357 Times Cited - Web of Science