The Nrf2-antioxidant Response Element Pathway: A Target for Regulating Energy Metabolism

J Nutr Biochem. 2012 Oct;23(10):1201-6. doi: 10.1016/j.jnutbio.2012.03.005. Epub 2012 Jul 21.

Abstract

The nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that responds to oxidative stress by binding to the antioxidant response element (ARE) in the promoter of genes coding for antioxidant enzymes like NAD(P)H:quinone oxidoreductase 1 and proteins for glutathione synthesis. The Nrf2/ARE pathway has nutritional interest owing to its activation by phytochemicals such as sulforaphane. Recently, the Nrf2 pathway was identified as having regulatory functions in mitochondrial biogenesis, adipocyte differentiation and liver energy metabolism. Activation of Nrf2 increases energy metabolism and conversely suppresses lipid synthesis. Lard-based, but not soybean oil-based, high-fat diets reduce mRNA expression of Nrf2 and its downstream targets, suggesting a macronutrient influence on the activation of the Nrf2 pathway and susceptibility to oxidative stress. This review examines data revealing the Nrf2 pathway's regulatory role in energy metabolism at the molecular, cellular and whole animal levels. Understanding the relationship of Nrf2 and energy metabolism in cells, tissues and physiologic systems will provide novel insights for nutritional interventions for obesity and its comorbidities such as diabetes.

Publication types

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

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Antioxidant Response Elements*
  • Cell Differentiation
  • Cell Line
  • Diet, High-Fat
  • Energy Metabolism / genetics*
  • Gene Expression Regulation
  • Humans
  • Liver / metabolism
  • Mitochondrial Turnover
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / genetics
  • Signal Transduction

Substances

  • NF-E2-Related Factor 2
  • NAD(P)H Dehydrogenase (Quinone)