Nitrated Fatty Acids – New Class of Signalling Molecules

Abstract

Nitrated lipids and fatty acids have recently emerged as a new class of signalling molecules in homeostasis regulation and in anti-inflammatory pathways in animals. This review summarizes the current knowledge and understanding of molecular mechanisms of their biosynthesis and signalling functions in animal cells. Nitrated fatty acids (NFA) represent a convergence of signalling pathways of oxidized lipids and nitric oxide NO). Nitration of fatty acids in vivo occurs either by the reaction of NO with lipid radicals or by the attack of reactive nitrogen species on intermediates of lipid oxidation with reactive oxygen species. NFA are highly stable in hydrophobic membrane lipids, which can serve as their reservoir. Biological functions of NFA could be derived from their decomposition producing NO. Due to their high reactivity with cell nucleophiles such as protein thiols, protein nitroalkenylation occurs, which considerably affects protein structure and activity. NFA are also endogenous ligands of peroxisome proliferator-activated receptors. Thus they are involved in the signalling pathways of this receptor in glucose homeostasis and adipocyte proliferation. NFA were also identified as mediators of anti-inflammatory signalling through their suppressive action on inflammatory stimuli. Despite recent advances in research on NFA, our understanding of signalling pathways and metabolism of NFA in vivo is still limited. Current research is focused on NFA as endogenous ligands and activators of peroxisome proliferator-activated receptor.