{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:42:13Z","timestamp":1791416533547,"version":"4.3.3"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,7,25]]},"abstract":"<jats:p>\n                    Omega-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 antiinflammatory 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 antiinflammatory 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-\u03baB activity and expression of TNF\u03b1, inducible NO synthase, and IL-1\u03b2, with enhanced mucoprotection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the\n                    <jats:italic>fat-1<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601280103","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:35:39Z","timestamp":1153182939000},"page":"11276-11281","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":331,"title":["Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis"],"prefix":"10.1073","volume":"103","author":[{"given":"Christian A.","family":"Hudert","sequence":"first","affiliation":[{"name":"*Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;"},{"name":"Department of Gastroenterology, Charit\u00e9 University Medicine, Virchow Campus, 13353 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten H.","family":"Weylandt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Charit\u00e9 University Medicine, Virchow Campus, 13353 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingdong","family":"Wang","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Hong","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, 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