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Title:   Author  item
                                            BRUINS, M - Leiden Universityitem
                                            DANE, A - Leiden Universityitem
                                            STRASSBURG, K - Leiden Universityitem
                                            VREEKEN, R - Leiden Universityitem
                                            Newman, Johnitem
                                            SALEM, JR, N - Columbia Universityitem
                                            TYBURCZY, C - Cornell Universityitem
                                            BRENNA, J - Cornell University
  Submitted to: Journal of Lipid Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/29/2013
                                    Publication  Date: 3/29/2013
                                    Citation: Bruins, M.J., Dane, A.D., Strassburg, K., Vreeken, R.J., Newman, J.W., Salem, Jr, N., Tyburczy, C., Brenna, J.T. 2013. Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets. Journal of Lipid Research. 54(6):1598-1607.Interpretive Summary: Dietary enrichment with the long chain omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to improve cognitive development in the young. Moreover, concentrations of lipid mediators formed from these omega-3 fatty acids are known to increase in adults when these lipids are increased in the diet.  To evaluate the responsiveness of these mediators in the young, the dose-response of plasma lipid mediators to key dietary omega-6 and omega-3 fatty acids were assessed in the pig, an important animal model for the study of human nutrition. Piglets were fed formula containing mixtures of arachidonic acid (ARA) and DHA from days 3 to 27 after birth, resulting in incremental intake (g/kg BW/d) of ARA: 0.5±0.0, 3.0±0.2, 3.9±0.2, 6.1±0.3 at constant DHA intake (5.9±0.4), or incremental intake of DHA: 1.9±0.2, 3.6±0.2, 5.8±0.3 at constant ARA intake (3.8±0.3). At day 28, plasma concentrations of non-esterified oxylipins and fatty acids were measured. ARA intake dose-dependently increased plasma ARA levels, as well as ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE), and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), both down stream metabolites of cytochrome P450 expoxygenase (CYP). Incremental DHA intake increased plasma DHA and most markedly raised the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). These CYP-dependent metabolites are important regulators of vasculature function and growth in many tissues. 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.
                                Technical Abstract: The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic (20:4n-6; ARA) and docosahexaenoic (22:6n-3; DHA) acid was determined in piglets. Piglets randomly received one of six formulas (n=8 per group) from day 3 to 27 postnatally. Diets contained varying ARA and DHA levels resulting in incremental intake (g/kg BW/d) of ARA: 0.5±0.0, 3.0±0.2, 3.9±0.2, 6.1±0.3 at constant DHA intake (5.9±0.4), or incremental intake of DHA: 1.9±0.2, 3.6±0.2, 5.8±0.3 at constant ARA intake (3.8±0.3). Plasma oxylipins concentrations and free plasma PUFA levels were determined at day 28 using LC-MS. Incremental dietary ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA dose-dependently increased ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE), and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), both  down stream metabolites of cytochrome P450 expoxygenase (CYP). ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE), which plays a role in retina vascularisation. 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.


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