The role of the Nrf2/Keap1 pathway in obesity and metabolic syndrome

Rev Endocr Metab Disord. 2015 Mar;16(1):35-45. doi: 10.1007/s11154-014-9305-9.


Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key regulator of antioxidant signaling that may prevent the development of metabolic syndrome and related cardiovascular diseases. However, emerging evidence shows that lack of Nrf2 could ameliorate insulin resistance, adipogenesis and adipocyte differentiation. Consistent with this, overexpression of Nrf2 gene could also cause insulin resistance under certain conditions. Furthermore, an increasing number of studies indicate that redox balance can be a critical element that contributes to the contradictory effects of Nrf2 on insulin sensitivity and resistance. Reactive oxygen species can promote normal insulin-mediated signal transduction under physiological conditions but also induce insulin resistance under certain pathological conditions. Therefore, the contradictory effects of Nrf2 on insulin signaling pathways may be related to its regulation of redox homeostasis. This review attempts to summarize the latest developments in our understanding of the mechanisms of Nrf2-mediated signaling and its role in the modulation of metabolic homeostasis.

Publication types

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

MeSH terms

  • Homeostasis / physiology
  • Humans
  • Insulin Resistance / physiology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • Metabolic Syndrome / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Obesity / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology*


  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species