title: Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets.
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.
authors.affiliation: DSM Biotechnology Center, Delft, The Netherlands.
authors.forename: Maaike J
authors.initials: MJ
authors.lastname: Bruins
authors.affiliation: Netherlands Metabolomics Centre (NMC), Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Adrie D
authors.initials: AD
authors.lastname: Dane
authors.affiliation: Netherlands Metabolomics Centre (NMC), Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Katrin
authors.initials: K
authors.lastname: Strassburg
authors.affiliation: Netherlands Metabolomics Centre (NMC), Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.affiliation: Obesity and Metabolism Research Unit, US Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.affiliation: DSM Nutritional Lipids, Columbia, MD; and.
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Tyburczy
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY. Electronic address: jtb4@cornell.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000494:pharmacology; D054883:Oxylipins / Q000097:blood*; D013552:Swine
chemical_list: C000602093:19,20-dihydroxydocosapentaenoic acid; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D054883:Oxylipins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System
keywords: eicosanoid; lipidomics; metabolomics; omega-3; omega-6 polyunsaturated fatty acid; prostaglandin
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