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

Abstract

Dietary intervention and genetic fat-1 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 fat-1 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 fat-1 mice, particularly for EPA (max. 1.7% in whole blood of fat-1 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 fat-1 mice. In plasma of n3-PUFA fed animals, EPA and DHA metabolites from the lipoxygenase and cytochrome P450 pathways dominated over ARA derived counterparts.Fat-1 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.

The Brain Oxylipin Profile Is Resistant to Modulation by Dietary n‐6 and n‐3 Polyunsaturated Fatty Acids in Male and Female Rats

“…Interestingly, serum has similarly high levels of ARA oxylipins, but very low levels of DHA oxylipins (Leng et al, , ). The rat whole brain oxylipin profile reported herein was similar to the female mouse whole brain profile (Ostermann et al, ). In all tissues, including the brain, the oxylipin levels do not necessarily reflect precursor PUFA levels, demonstrating that PUFA levels cannot be used to predict oxylipin levels and need to be measured directly.…”

“…Fifth, different solid phase extraction methods vary in their efficacy of oxylipin extraction; however, the method used in this study is the most efficient in general, although some of the ARA-derived CYP oxylipins may not be extracted as well as by other procedures Puppolo et al, 2014). This may explain why fewer of these metabolites were observed in the whole rat brain herein, compared to whole mouse brain (Ostermann et al, 2017b). Finally, the levels of PUFA in the control, LNA, and LNA + ALA diets are within the ranges found in human diets, but the n-3 PUFA added to the ALA, EPA, and DHA levels would be more difficult to attain without supplementation.…”

A single meal has the potential to alter brain oxylipin content

“…In conclusion, while it has previously been shown that the oxylipin content of the brain can be modified by changes in the composition of a chronically consumed diet [12][13][14][15][16][17], in this study we demonstrate that a single meal exposure is sufficient to produce differences in oxylipin content. We also demonstrate that fasting alters brain oxylipin content.…”

“…In previous work conducted in our laboratory, we found that the consumption of a Western diet over the period of three months increased arachidonic acid derived oxylipins and altered the fatty acid profiles of the brains of mice [12]. Further, others have shown that various modifications of a chronically consumed diet have the potential to modify brain oxylipin levels [13][14][15][16][17].…”

Effect of dietary EPA and DHA on murine blood and liver fatty acid profile and liver oxylipin pattern depending on high and low dietary n6-PUFA

“…15 For example, in mice and rats dietary EPA and DHA induced a shift in the overall tissue oxylipin profile by decreasing ARA derived oxylipins and increasing n3-PUFA derived oxylipins. 16,17 Several oxylipins synthesized from EPA or DHA exert less inflammatory activity compared to those from ARA, e.g. EPA derived LTB 5 vs. ARA derived LTB 4 18 or are directly involved in the resolution of inflammation, e.g.…”