Healthy Omega-3 Fatty Acid Metabolites

Omega-3 fatty acids found in seafood and nuts or taken as dietary supplements have health benefits that include preventing cardiovascular disease and reducing inflammation. But the biochemical basis for these benefits has not been well understood. Bruce A. Freeman and Francisco J. Schopfer of the University of Pittsburgh and coworkers have now identified omega-3 fatty acid metabolites that may be responsible for the favorable effects and show how drugs such as aspirin can boost levels of the compounds (Nat. Chem. Biol., DOI: 10.1038/nchembio.367). The metabolites—a class of electrophilic oxo derivatives that the researchers call EFOXs—are produced by the action of the enzyme cyclooxygenase-2 (COX-2) on omega-3 fatty acids in macrophages. EFOXs bind to transcriptional regulatory proteins, and the resulting alterations in gene expression patterns have beneficial metabolic and anti-inflammatory effects. The COX-2 inhibitor aspirin induces the enzyme to produce greater than normal quantities of EFOXs, enhancing the effects. The findings suggest that EFOXs “are signaling mediators that transduce the beneficial clinical effects of omega-3 fatty acids, COX-2, and aspirin,” the researchers write.