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

Cynthia Tyburczy,Maaike J. Bruins,J.Thomas Brenna,Katrin Strassburg,Adrie D. Dane,Norman Salem,Rob J. Vreeken,John W. Newman

doi:10.1194/jlr.m034918

Abstract

The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62, resulting in incremental intake (g/kg BW/day) of ARA: 0.07 ± 0.01, 0.43 ± 0.03, 0.55 ± 0.03, and 0.82 ± 0.05 at constant DHA intake (0.82 ± 0.05), or incremental intake of DHA: 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 at constant ARA intake (0.54 ± 0.04). Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dose-dependently 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 influenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these findings remains to be determined.

Highlights

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
The significant increase in plasma DHA, linoleic acid, and ␣-linolenic acid levels that occurred with increasing arachidonic acid (ARA) intake disappeared after correcting for multiple testing (Table 1)
The three dietary DHA levels resulted in a mean DHA intake of 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 g/kg body weight (BW)/day, respectively, at constant ARA intake (0.54 ± 0.04 g/kg BW/day) over the 24 days of feeding

Summary

Introduction

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. 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. The polyunsaturated fatty acids linoleic acid, dihomo-␥-linolenic acid (20:3n-6; DGLA), ARA, ␣-linolenic acid, eicosapentaenoic acid (20:5n-3; EPA), and DHA are the main precursors for various oxylipins [19]. The three primary enzymes catalyzing the oxygenation of these fatty acids into oxylipins are the cytochrome P450 expoxygenases (CYP), cyclooxygenases (COX), and lipoxygenases (LOX) [19]. Other enzymes, such as soluble epoxide hydrolases (sEH), can further metabolize some of the oxylipin species

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