Endogenous Generation and Signaling Actions of Omega-3 Fatty Acid Electrophilic Derivatives

Biomed Res Int. 2015:2015:501792. doi: 10.1155/2015/501792. Epub 2015 Aug 3.

Abstract

Dietary omega-3 polyunsaturated fatty acids (PUFAs) are beneficial for a number of conditions ranging from cardiovascular disease to chronic airways disorders, neurodegeneration, and cancer. Growing evidence has shown that bioactive oxygenated derivatives are responsible for transducing these salutary effects. Electrophilic oxo-derivatives of omega-3 PUFAs represent a class of oxidized derivatives that can be generated via enzymatic and nonenzymatic pathways. Inflammation and oxidative stress favor the formation of these signaling species to promote the resolution of inflammation within a fine autoregulatory loop. Endogenous generation of electrophilic oxo-derivatives of omega-3 PUFAs has been observed in in vitro and ex vivo human models and dietary supplementation of omega-3 PUFAs has been reported to increase their formation. Due to the presence of an α,β-unsaturated ketone moiety, these compounds covalently and reversibly react with nucleophilic residues on target proteins triggering the activation of cytoprotective pathways, including the Nrf2 antioxidant response, the heat shock response, and the peroxisome proliferator activated receptor γ (PPARγ) and suppressing the NF-κB proinflammatory pathway. The endogenous nature of electrophilic oxo-derivatives of omega-3 PUFAs combined with their ability to simultaneously activate multiple cytoprotective pathways has made these compounds attractive for the development of new therapies for the treatment of chronic disorders and acute events characterized by inflammation and oxidative stress.

Publication types

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

MeSH terms

  • Antioxidants / metabolism*
  • Antioxidants / therapeutic use
  • Diet
  • Dietary Supplements
  • Fatty Acids, Omega-3 / chemistry
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / therapeutic use
  • Humans
  • Inflammation / diet therapy
  • Inflammation / genetics
  • Inflammation / metabolism*
  • NF-E2-Related Factor 2 / biosynthesis
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / genetics
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • PPAR gamma / biosynthesis
  • PPAR gamma / metabolism
  • Signal Transduction / drug effects

Substances

  • Antioxidants
  • Fatty Acids, Omega-3
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • PPAR gamma