Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets

Abstract

Human milk contains the essential fatty acids linoleic acid (18:2n-6) and ␣ -linolenic acid (18:3n-3) and their respective n-3 and n-6 long-chain polyunsaturated fatty acid (LCPUFA) metabolites. Arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) are the most abundant LCPUFA in human milk ( 1 ). DHA and ARA accumulate in brain and retina at a high rate during the last trimester of pregnancy and the fi rst months of life ( 2 ). DHA and ARA may be synthesized in the body from the precursor essential fatty acids, ␣ -linolenic acid (18:3n-3; ALA) and linoleic acid (18:2n-6; LA), respectively. However, the endogenous conversion effi ciency of these precursor fatty Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dosedependently increased plasma ARA levels. In parallel, ARA intake dose-dependently increased ARA-derived diols 5,6-and 14,15-dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450 expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18-dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA intake dose-dependently infl uenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these fi ndings remains to be determined. -Bruins, M.

A Protective Lipidomic Biosignature Associated with a Balanced Omega-6/Omega-3 Ratio in fat-1 Transgenic Mice

“…Our study highlighted a significant difference in the omega-6/omega-3 ratio between unesterified plasma lipids and other previously reported tissues [3], [15], [16]. In particular, our results showed a marked increase for unesterified EPA compared to unesterified DHA in the plasma of fat-1 mice (Table 1), which could be explained, in part, by a retroconversion of DHA to EPA [31]–[37]. The concomitant elevation of the DHA-containing phospholipids, however, suggests that EPA might be a preferred substrate for the hydrolytic activity of phospholipase A 2 (PLA 2 ) in plasma, rather than DHA [44].…”

Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism

“…Although DHETs are released into the extracellular fluid, endothelial cells can incorporate small amounts of DHETs into phosphatidylcholine and phosphatidylinositol [50]. DHETs and diols formed from EpETEs and EpDPEs also are present in rodent brain and spinal cord [16,51], as well as in the plasma of humans and piglets fed ω-3 PUFA supplements [26,52]. …”

Cross-Classification of Human Urinary Lipidome by Sex, Age, and Body Mass Index

“…Lipid mediators include polyunsaturated fatty acids (PUFAs), lysophosphatidic acid, and their derivatives. It is believed that many regulatory activities of PUFAs are mediated by their oxidation products, oxylipins [8], which are produced and activated by several enzymes such as cytochrome P450 (P450), cyclooxygenases (COX), and lipoxygenases (LOX). Oxylipins have been mostly associated with the initiation and resolution of inflammation and vascular function.…”