We all know about fatty acids,

but what about oxylipins?

Published October 01 2017

Whether you know fatty acids as the essential nutrients your doctor tells you to eat or as the hydrocarbon chains that terminate in a carboxyl group, you undoubtedly know they are important. But recent research in rats indicates that particular derivatives of fatty acids, known as oxylipins, may also play important roles in the body as the main mediators of the effects of polyunsaturated fatty acids.

A recent paper in the Journal of Lipid Research describes one of the first studies to profile oxylipins, which are oxygenated products of fatty acids. Only within the past decade have mass spectrometry and liquid chromatography become effective enough to study oxylipins.

“There is a lot of literature out there on fatty acid composition, and we tend to make conclusions based on this, but we can’t necessarily do that,” said Harold Aukema, an author of the paper and professor at the University of Manitoba in Winnipeg, Canada. “For instance, the proportion of oxylipins is much different than the proportion of their precursor fatty acids in the tissues.”

Aukema’s research has focused on examining dietary components of kidney health and signaling molecules in the kidneys. His interests include the “physiologic and metabolic basis of dietary recommendations for dietary protein and for omega-3 fatty acids.” This isn’t his first paper on oxylipins. Among others, in 2015 he authored a paper that reviewed the roles of oxylipins such as prostaglandins, neuroprotectins and maresins.

In the recent paper, Aukema’s team reports on how diets with moderately increased levels of two fatty acids, linoleic acid, or LA, and alpha-linoleic acid, or ALA, affected the percentages of oxylipins in rat kidneys, livers and blood serum.

LA, an omega-6 polyunsaturated fatty acid, or PUFA, is one of the main fatty acids we consume. ALA is an omega-3 PUFA and is plant-derived. Once consumed, LA and ALA produce a large portion of the oxylipins in our bodies. Omega-6 fatty acids tend to increase inflammation in the body despite benefits such as decreasing blood lipids. Omega-3 fatty acids tend to decrease inflammation.

Distribution of oxylipin and fatty acid mass in kidney, liver and serum of rats provided the control diet. Data are from female and male rats combined. Abbreviations: AA=arachidonic acid, ALA=alpha-linolenic acid, EPA= eicosapentaenoic acid, DHA=docosahexaenoic acid, LA=linoleic acid, n-6=omega-6.image courtesy of the University of Manitoba

Although our bodies use fatty acids to produce oxylipins, the fatty acid composition of our bodies doesn’t necessarily reflect the oxylipin composition. To understand this relationship, the study looked at three groups of rats: a control group, a group fed higher LA, and a group fed both higher LA and ALA but in a ratio similar to that of the control group. The role of the diet with both LA and ALA was to determine whether the omega-3 PUFA ALA would mitigate the effects of the increased omega-6 PUFA LA.

The ratio of omega-6 to omega-3 PUFA is too high in modern diets, Aukema said. “The lower (the ratio)the better, at least 5-to-1, and possibly lower.” In one model, this ratio increased from 5.4 in the year 1909 to 9.6 in 1999. The recommended amount of omega-6 PUFA isn’t set. The 2015 Dietary Reference Intake Report for fatty acids recommends five to 10 percent of our energy come from omega-6 PUFA for optimal health, while the American Heart Association recommends more.

Many fatty acids confer benefits without being sequestered in tissues. However, fatty acids could affect the body through oxylipins. “You can’t just say, ‘If fatty acids don’t change (in the body), then the oxylipins won’t change,’” Aukema said.

In the study, Aukema increased the rats’ dietary LA from two to five grams per 100 grams of food. In the LA group, LA-derived oxylipins increased in the kidneys by 84 percent, in the liver by 175 percent and in serum by 75 percent. Oxylipins from arachidonic acid, or AA, (another omega-6 derived from LA) also increased in kidney and liver. Importantly, in several cases, the increases in oxylipins occurred even when the levels of their fatty acid precursors did not change.

In the rats fed both LA and ALA, fewer types of omega-6 oxylipins were elevated, indicating potential mitigating effects of omega-3 PUFA on omega-6 PUFA. The ratio of the omega-6 to omega-3 PUFA and their oxylipins also was comparable to that in the control group. In contrast, the rats fed a diet of LA alone showed the ratio of omega-6 to omega-3 oxylipins increase by as much as 96 percent.

Philip C. Calder, a professor of nutritional immunology at the University of Southampton in Southampton, England, has done research of his own on the inflammatory processes of omega-3, or n-3, fatty acids. Calder said research already has shown that “n-6 PUFA intake has increased over the last 40 years or so, especially in the U.S., as n-6 PUFA have permeated the food chain. Some argue this is a bad thing because n-6 PUFA are generally pro-inflammatory, as this paper demonstrates. So one conclusion of this paper might be that we need to be cautious about increasing intake of n-6 PUFA further.”

The next step includes understanding more of these oxylipins and how they interact both with each other and with their fatty acid precursors. Future experiments might delineate the relative functions and biopotencies of the oxylipins as well helping us understand how they interact.

“I don’t think we should focus exclusively on either,” Aukema said. “Fatty acids do more than get converted to oxylipins. While one of the main ways they affect things is through the production of oxylipins, they add important information.” He said this work is a fundamental study. “Now that we have a better idea of the spectrum that is present, we can start to examine more their functions and how they interact.”

Lily Williams Lily Williams has a B.A. in ecology, evolution and organismal biology from Vanderbilt University and an M.S. in science, health and environmental journalism from Medill School of Journalism at Northwestern University. She is a freelance journalist and communications director based in Asheville, N.C.