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Title:   Author  item
                                            WATKINS, BRUCE - University Of Californiaitem
                                            KIM, JEFFREY - University Of Californiaitem
                                            KENNY, ANNE - University Of Connecticutitem
                                            Pedersen, Theresaitem
                                            PAPPAN, KIRK - Metabolon, Incitem
                                            Newman, John
  Submitted to: BBA Molecular and Cell Biology of Lipids
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/19/2016
                                    Publication  Date: 7/21/2016
                                    Citation: Watkins, B.A., Kim, J., Kenny, A., Pedersen, T.L., Pappan, K.L., Newman, J.W. 2016. Circulating levels of endocannabinoids and oxylipins altered by dietary lipids in older women are likely associated with previously identified gene targets. BBA Molecular and Cell Biology of Lipids. 1861(11). doi: 10.1016/j.bbalip.2016.07.007.Interpretive Summary: Postmenopausal women (PMW) report marginal intakes of omega-3 polyunsaturated fatty acids (n-3 PUFA) either from cold water fish or supplements, and these women are at risk of chronic diseases associated with the skeletal, muscular, and cardiovascular systems. In a group of white PMW (75 ± 7 y) randomized in a double-masked manner, we characterized the impact of 6 mo of fish oil supplementation containing n-3 PUFAs (720 mg EPA + 480 mg DHA/d, n=20) or placebo (1.8g oleic acid/d, n=20) on a broad array of metabolites in serum.  Changes in lipid mediators including the weight/energy/inflammation modulating endocannabinoids (EC), the inflammation/vascular tone/cell growth regulating oxylipins (OL), and a “global” assessment of central metabolism (GM) were determined using ultra performance liquid chromatography-tandem mass spectrometry for ECs and OLs, and by gas chromatography mass spectrometry (GC-MS) and LC-MS/MS for GMs. EPA and DHA in plasma increased in PMW supplemented with fish oil and the magnitudes of PUFA changes in EC and OL levels were influenced by baseline n-3 PUFA status. The n6-acyl-ethanolamides, a class of ECs, and arachidonate-derived diols were decreased, while EPA and DHA diols, epoxides, and alcohols were increased in PMW supplemented with fish oil. GM analysis revealed that n-3 PUFA supplementation also increased renal steroid hormone and proteolytic metabolite levels in PMW. Herein, the levels of EC, OL, and GM in PMW demonstrated responses to 6 mo of n-3 PUFA. This study shows phenotypic responses to n-3 PUFA in PMW and potential indicates possible clinical considerations of fish oil actions on EC and OL metabolism.
                                Technical Abstract: Postmenopausal women (PMW) report marginal n-3 PUFA intakes and are at risk of chronic diseases associated with the skeletal, muscular, and cardiovascular systems. Our investigation characterized the endocannabinoids (EC), oxylipins (OL), and global metabolites (GM) in white PMW (75 ± 7 y), randomized in a double-masked manner, from baseline to 6 mo after receiving a fish oil supplement of n-3 PUFA (720 mg EPA + 480 mg DHA/d, n=20) or placebo (1.8g oleic acid/d, n=20). EC and OL levels in serum were determined using UPLC-MS/MS and for GM by GC-MS and LC-MS/MS. EPA and DHA in plasma increased in PMW supplemented with fish oil and the magnitudes of PUFA changes in EC and OL levels were influenced by baseline n-3 PUFA status. EC n-6 acyl-ethanolamides, arachidonate-derived diols were decreased and EPA and DHA diols, epoxides, and alcohols were increased in PMW supplemented with fish oil. GM analysis revealed that n-3 PUFA supplementation increased renal steroid hormone and proteolytic metabolite levels in PMW. Herein, the levels of EC, OL, and GM in PMW demonstrated responses to 6 mo of n-3 PUFA. This study shows phenotypic responses to n-3 PUFA in PMW and potential clinical considerations of actions on EC and OL.


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