Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.24.311985v1?rss=1 Authors: Snyder, N. W., Singh, B., Buchan, G., O'Brien, J., Arroyo, A. D., Liu, X., Sobol, R. W., Blair, I. A., Mesaros, C. A., Wendell, S. G. Abstract: Metabolism of PUFA results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, ,{beta}-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETEs) and mono-saturated metabolites of 15-oxoETE and 17-oxoDHA in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase, known for its reduction of the ,{beta}-unsaturated double bond, was not responsible for saturation of oxo-fatty acids. Surprisingly, the knock down of prostaglandin reductase by shRNA confirmed its participation in the formation of 15-oxoETE and 17-oxoDHA mono-saturated metabolites. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties. Copy rights belong to original authors. Visit the link for more info