Dietary Linoleic Acid (LA) Increases Linoleic and Arachidonic Acid (ARA) Derived Bioactive Lipids, Despite Not Altering Tissue Fatty Acid Levels
Authors: Leng Shan M. , Aukema Harold M. 
Published: November 2023

BackgroundDietary recommendations for reducing cardiovascular disease risk include the recommendation to increase intake of polyunsaturated fatty acids. However, whether increased linoleic acid (LA) should be included in this remains controversial. Concerns that this n‐6 fatty acid may increase inflammation have been countered by evidence that dietary LA intake does not alter the levels of arachidonic acid (ARA), the precursor of pro‐inflammatory eicosanoids. However, the effect of dietary LA on these ARA derived oxylipins is not known. Furthermore, LA also can be converted to bioactive lipids that also appear to have pro‐inflammatory effects, but there is little information on these oxylipins. With recent advances in lipidomics, over 150 of these bioactive lipids (oxylipins) can now be analyzed by HPLC/MS/MS. The objective of the current study therefore was to examine the effect of dietary LA level on LA and ARA oxylipins in normal rat liver, kidney and serum.MethodsWeanling Sprague‐Dawley rats were provided diets based on the AIN93G diet for laboratory rodents. The isocaloric and isolipidic diets had oils (soy, olive, safflower) containing adequate levels of LA (2.1 g/100 g diet) or higher LA (5 g/100 g diet), with the higher LA replacing monounsaturated fatty acids. Male and female rats were provided the diets ad libitum for 6 weeks, after which livers, kidneys and serum were collected for oxylipin analysis. Phospholipid fatty acids were purified from lipid extracts using TLC and quantified as fatty acid methyl esters by GLC. Oxylipins were extracted in methanolic solutions containing deuterated internal standards. After solid phase extraction, >150 oxylipins were screened by HPLC/MS/MS, and those above the limit of quantification (LOQ) were quantified using the stable isotope dilution method. Of ~100 oxylipins above the LOQ in each tissue, ~10 and ~50 were derived from LA and ARA, respectively.ResultsProviding a diet with oils higher in LA resulted in higher phospholipid LA and ARA concentrations in the livers, but not in the kidneys or serum. However, there were LA and ARA oxylipins that were higher in all 3 tissues in rats provided the high LA diet. In the liver, 8 LA oxylipins and 13 ARA oxylipins were (~50%–300%) higher in rats provided the high LA diet. In kidney, despite no increase in LA or ARA levels, all LA oxylipins detected and 23 ARA oxylipins were (~50%–200%) higher. Similarly in serum, 9 LA oxylipins and 2 ARA oxylipins were (~50%–200%) higher in rats provided the high LA diet. Similar discrepant effects were observed with sex, as 45 ARA oxylipins from the 3 tissues were higher in males compared to females, despite not having higher ARA levels.ConclusionsThese results illustrate that although dietary LA may not alter the concentrations of LA and ARA, it does increase the levels of bioactive lipids derived from both LA and ARA in rat tissues. Similarly, sex effects on ARA oxylipins are not reflected in ARA levels in in these tissues. In conclusion, dietary advice to increase LA intake may need to be re‐considered in light of its effect on the production of pro‐inflammatory bioactive lipids from both LA and ARA.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC)