Hudert, Christian A.Weylandt, Karsten H.Lu, YanWang, JingdongHong, SongDignass, AxelSerhan, Charles N.Kang, Jing X.2019-10-052006Hudert, C. A., K. H. Weylandt, Y. Lu, J. Wang, S. Hong, A. Dignass, C. N. Serhan, and J. X. Kang. 2006. “Transgenic Mice Rich in Endogenous Omega-3 Fatty Acids Are Protected from Colitis.” Proceedings of the National Academy of Sciences 103 (30): 11276–81. https://doi.org/10.1073/pnas.0601280103.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483504Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are the precursors of potent lipid mediators and play an important role in regulation of inflammation. Generally, n-6 PUFA promote inflammation whereas n-3 PUFA have anti inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived proinflammatory eicosanoids. Newly discovered resolvins and protectins are potent antiinflammatory-lipid mediators derived directly from n-3 PUFA with distinct pathways of action. However, the role of the n-3 PUFA tissue status in the formation of these antiinflammatory mediators has not been addressed. Here we show that an increased n-3 PUFA tissue status in transgenic mice that endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant formation of anti inflammatory resolvins and effective reduction in inflammation and tissue injury in colitis. The endogenous increase in n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid mediators such as leukotriene B4 and prostaglandin E2. The observed inflammation protection might result from decreased NF-kappa B activity and expression of TNF alpha, inducible NO synthase, and IL-1 beta, with enhanced muco-protection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the fat-1 transgenic mouse as a new experimental model for the study of n-3 PUFA-derived lipid mediators. They add insight into the molecular mechanisms of inflammation protection afforded by n-3 PUFA through formation of resolvins and protectins other than inhibition of n-6 PUFA-derived eicosanoid formation.en-USJournal Article2019-10-0510.1073/pnas.0601280103