Key Findings:
Oxylipins constitute a family of oxygenated products which are formed from fatty acids. Many of oxylipins have metabolic significance. In this study, oxylipin profiles of rat kidney, liver and serum are described. Although large changes in dietary LA have been shown to alter LA oxylipin production, the current study demonstrates that more moderate differences in dietary LA also affect LA oxylipins. Dietary LA levels were 4.7% in the adequate diet and 11.4-11.8% in the LA and LA+ALA diets, similar to the 5-10% of energy range of dietary LA that is recommended by the Institute of Medicine. It was shown that dietary LA changes around the normal range of intake levels influences LA oxylipins, even when tissue LA levels may not be altered. Increased dietary LA within the usual dietary range resulted in higher levels of 10-12 AA oxylipins in kidney and liver, as well as many LA, GLA, EDA, and DGLA oxylipins in these tissues, and LA oxylipins in serum. The current study reveals that AA and other n-6 PUFA derived oxylipins with generally pro-inflammatory effects are elevated in tissues of normal rats provided a higher LA diet. Higher dietary LA also resulted in lower levels of a small number of n-3 PUFA derived oxylipins. Higher n-3 derived oxylipins in kidneys from rats given the LA+ALA diets compared to both the control and the LA groups resulted in higher levels of not only ALA, but also EPA and DHA oxylipins (despite no differences in EPA or DHA) were found. Approximately 40% of all oxylipins detected in the current analysis displayed sex effects, and of these, ~90% were higher in males. Much higher renal DHA levels in female kidneys was associated with higher DHA oxylipins. The n-3/n-6 oxylipin ratios were higher than the precursor n-3/n-6 PUFA ratios, indicating increased conversion and/or decreased degradation of n-3 compared to n-6 oxylipins, relative to their precursor PUFA. Thus, dietary LA increases many LA and AA oxylipins and reduces some n-3 PUFA derived oxylipins, and dietary ALA mitigates many of these effects. Higher levels of oxylipins in male rats may have important physiological effects that remain to be elucidated. Tissue n-3 compared to n-6, and C18 compared to C20 and C22 PUFA, appear to increase oxylipins more efficiently in vivo. Blood oxylipin profiles do not necessarily reflect tissue profiles, which has implications for human studies that typically utilize blood as the primary and often only tissue sampled.
ABSTRACT
A vast literature on fatty acids in mammals exists, but comparable compositional data on oxylipins is lacking. Weanling Sprague-Dawley rats were therefore provided control diets or diets with higher linoleic acid (LA), or with higher LA and α-linolenic acid (LA+ALA) for six weeks. Kidneys, livers and serum were analyzed for oxylipins and fatty acids. The proportion of tissue oxylipins derived from LA was greater than the relative proportion of LA itself, while arachidonic acid (AA) oxylipins were overrepresented in serum. Higher dietary LA increased kidney LA and AA oxylipins, despite not altering LA or AA. In liver, both LA and AA and their oxylipins were higher, while in serum only LA oxylipins were higher with higher dietary LA. Higher LA resulted in a higher ratio of n-6/n-3 PUFA derived oxylipins; adding ALA to the LA diet mitigated this and many, but not all effects of the LA diet. ~40% of oxylipins detected were influenced by sex, and unlike their PUFA precursors, most (>90%) of these were higher in males. These differences in dietary LA and sex on oxylipin and fatty acid profiles furthers our understanding of the effects of fatty acids and may have implications for dietary LA recommendations.
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