Nitrated fatty acids: from diet to disease

Fatty acids not only provide caloric energy in our diets and building blocks of lipids but are also precursors of potent signaling molecules. Fatty acids can undergo enzymatic and non-enzymatic transformations to form autocrine and paracrine signaling molecules that regulate energy balance and metabolic homeostasis. A new class of lipid signaling mediators known as nitro-fatty acids (NO₂-FAs) has recently been identified. These NO₂-FAs are generated endogenously through non-enzymatic reactions of secondary products of nitrite and nitric oxide and are readily detected in human plasma and urine. NO₂-FAs are potent anti-inflammatory and antioxidant cell signaling mediators and exert protective effects in numerous pre-clinical animal models of disease including cardiovascular, pulmonary and renal fibrosis. Chronic unresolved inflammation is common key feature underlying most fibrotic disorders. Two pathways that converge on inflammation and oxidative stress are nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor kappa B (NF-κB). NO₂-FAs are pleiotropic signaling modulators that target both of these pathways providing a therapeutic strategy directed towards an integrated decrease in inflammation. This review summarizes the latest findings and understanding of the formation, signaling and anti-fibrotic effects of NO₂-FA.