Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis

Antioxid Redox Signal. 2017 Apr 1;26(10):519-541. doi: 10.1089/ars.2016.6776. Epub 2016 Aug 30.


Significance: Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manifestation.

Critical issues: The purpose of this article is to summarize recent developments in the understanding of NAFLD, essentially focusing on OxS as a major pathogenetic mechanism. Various attempts to translate reactive oxygen species (ROS) scavenging by antioxidants into experimental and clinical studies have yielded mostly encouraging results.

Future directions: Although augmented concentrations of ROS and faulty antioxidant defense have been associated to NAFLD and related complications, mechanisms of action and proofs of principle should be highlighted to support the causative role of OxS and to translate its concept into the clinic. Antioxid. Redox Signal. 26, 519-541.

Keywords: antioxidants; cardiometabolic disorders; liver steatosis; mitochondria; reactive oxygen species; treatment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Biomarkers
  • Endoplasmic Reticulum Stress
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Gene Expression Regulation
  • Hepatitis / etiology
  • Hepatitis / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism
  • MicroRNAs / genetics
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mutation
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Peroxidase / metabolism
  • Reactive Oxygen Species / metabolism


  • Antioxidants
  • Biomarkers
  • Lipoproteins, LDL
  • MicroRNAs
  • Reactive Oxygen Species
  • oxidized low density lipoprotein
  • Peroxidase