Key Points
One of the main ways in which ALA may mediate its effects is via oxygenated metabolites, called oxylipins, that are produced via cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) pathways. The current study assessed the effects of ALA, EPA and DHA and of sex on oxylipins in normal rat kidney, liver and serum. Higher levels of ALA and EPA oxylipins in response to dietary ALA were observed and related to the concomitant increases in
their PUFA precursors, but the higher DHA oxylipins in the kidney and serum occurred despite lower (kidney) or unchanged (serum) DHA levels. The data demonstrate the differing effects of dietary ALA, EPA and DHA on the oxylipin profile in rat kidney, liver and serum. These fundamental data show that each fatty acid increases the n-3 oxylipins directly formed from that fatty acid more than any other n-3 oxylipins. However, ALA can also be converted to EPA and DHA oxylipins, and DHA can be retroconverted to EPA oxylipins, while conversion of EPA to DHA oxylipins and retroconversion of DHA and EPA to ALA oxylipins may be limited. Additionally, AA and other n-6 oxylipins are reduced in all three sites, and LA oxylipins in the liver are increased by dietary n-3 PUFA in the following order of efficacy: DHA > EPA > ALA. Males generally have higher levels of oxylipins in all three sites. However, exceptions to the general patterns of fatty acids and sex effects demonstrate that oxylipins do not necessarily reflect PUFA levels. These findings highlight the need for greater understanding of the
functions of oxylipins both individually and in combination in the context of tissue-specific profiles and have implications for human studies that are limited to fatty acid composition data in blood.
ABSTRACT
There is much data on the effects of dietary n-3 fatty acids on tissue fatty acid compositions, but comparable comprehensive data on their oxygenated metabolites (oxylipins) is limited. The effects of providing female and male rats with diets high in α-linolenic acid (ALA), EPA or DHA for 6 weeks on oxylipins and fatty acids in kidney, liver and serum were therefore examined. The oxylipin profile generally reflected fatty acids, but it also revealed unique effects of individual n-3 fatty acids that were not apparent from fatty acid data alone. Dietary ALA increased renal and serum DHA oxylipins even though DHA itself did not increase, while dietary EPA did not increase DHA oxylipins in kidney or liver, suggesting that high EPA may inhibit this conversion. Oxylipin data generally corroborated fatty acid data that indicated that DHA can be retroconverted to EPA and that further retroconversion to ALA is limited. Dietary n-3 fatty acids decreased n-6 fatty acids and their oxylipins (except linoleic acid and its oxylipins), in order of effectiveness of DHA N EPA N ALA, with some exceptions: several arachidonic acid oxylipins modified at carbon 15were not lower in all three sites, and EPA had a greater effect on 12-hydroxy-eicosatetraenoic acid and its metabolites in the liver. Oxylipins were predominantly higher in males, which was not reflective of fatty acids. Tissue-specific oxylipin profiles, therefore, provide further information on individual dietary n-3 fatty acid and sex effects that may help explain their unique physiological effects and have implications for dietary recommendations.