Omega-3 fatty acids (fish oils) protect against colitis (at least in mice!)

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Proc. Natl. Acad. Sci. U.S.A. Jul 17 [Epub ahead of print] (2006)

Transgenic mice rich in endogenous omega-3 fatty acids are protected

from colitis.

Hudert CA, Weylandt KH, Lu Y, Wang J, Hong S, Dignass A, Serhan CN,

Kang JX

Department of Medicine, Massachusetts General Hospital and Harvard

Medical School, Boston, MA 02114; Department of Gastroenterology,

Charité University Medicine, Virchow Campus, 13353 Berlin, Germany;

and Center for Experimental Therapeutics and Reperfusion Injury,

Brigham and Women's Hospital, Harvard Medical School, Boston, MA

02115

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-kB activity and expression of TNFa, inducible NO

synthase, and IL-1, 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 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.

Dave

(father of (21); PSC 07/03; UC 08/03)