Modulation of the endogenous omega-3 fatty acid and oxylipin profile <i>in vivo</i>—A comparison of the <i>fat-1</i> transgenic mouse with C57BL/6 wildtype mice on an omega-3 fatty acid enriched diet

<div><p>Dietary intervention and genetic <i>fat-1</i> mice are two models for the investigation of effects associated with omega-3 polyunsaturated fatty acids (n3-PUFA). In order to assess their power to modulate the fatty acid and oxylipin pattern, we thoroughly compared <i>fat-1</i> and wild-type C57BL/6 mice on a sunflower oil diet with wild-type mice on the same diet enriched with 1% EPA and 1% DHA for 0, 7, 14, 30 and 45 days. Feeding led after 14–30 days to a high steady state of n3-PUFA in all tissues at the expense of n6-PUFAs. Levels of n3-PUFA achieved by feeding were higher compared to <i>fat-1</i> mice, particularly for EPA (max. 1.7% in whole blood of <i>fat-1</i> vs. 7.8% following feeding). Changes in PUFAs were reflected in most oxylipins in plasma, brain and colon: Compared to wild-type mice on a standard diet, arachidonic acid metabolites were overall decreased while EPA and DHA oxylipins increased with feeding more than in <i>fat-1</i> mice. In plasma of n3-PUFA fed animals, EPA and DHA metabolites from the lipoxygenase and cytochrome P450 pathways dominated over ARA derived counterparts.<i>Fat-1</i> mice show n3-PUFA level which can be reached by dietary interventions, supporting the applicability of this model in n3-PUFA research. However, for specific questions, e.g. the role of EPA derived mediators or concentration dependent effects of (individual) PUFA, feeding studies are necessary.</p>