title: Circulating levels of endocannabinoids and oxylipins altered by dietary lipids in older women are likely associated with previously identified gene targets.
abstract: Postmenopausal women (PMW) report marginal n-3 PUFA intakes and are at risk of chronic diseases associated with the skeletal, muscular, neuroendocrine, and cardiovascular systems. How n-3 PUFA affect the amounts of endocannabinoids (ECs) and oxylipins (OLs) of metabolic and physiologic importance in PMW is not clear. Based on our recent findings that dietary n-3 PUFA alter gene targets of the EC system and lower pro-inflammatory OL we proceeded to characterize these actions in blood of PMW. Our aim was to determine levels of the ECs, OLs, and global metabolites (GM) in white PMW (75±7y), randomized in a double-masked manner, from baseline to 6mo after receiving a fish oil supplement of n-3 PUFA (720mg 20:5n3+480mg 22:6n3/d, n=20) or placebo (1.8g oleic acid/d, n=20). ECs and OLs in serum were determined by UPLC-MS/MS and GM by GC-MS and LC-MS/MS. Plasma 20:5n3 and 22:6n3 levels increased in PMW given fish oil. EC n-6 acyl-ethanolamides, arachidonate-derived diols were decreased and 20:5n3 and 22:6n3 diols, epoxides, and alcohols were increased in PMW given fish oil. GM analysis revealed that n-3 PUFA supplementation increased renal steroid hormone and proteolytic metabolite levels in PMW. Herein, we confirm that gene targets of the EC system, previously found as modifiable by n-3 PUFA result in changes in the levels of ECs and OLs in PMW. This study shows phenotypic responses (in levels) to n-3 PUFA supplementation in PMW and increases of n-3 acyl-ethanolamide and n-3-derived OL of clinical considerations in aging.
authors.affiliation: Department of Nutrition, University of California, Davis, Davis, CA, United States; Center on Aging, University of Connecticut Health Center, Farmington, CT, United States. Electronic address: baw@purdue.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Watkins
authors.affiliation: Genome and Biomedical Sciences Facility, University of California, Davis, Davis, CA, United States. Electronic address: jefkim@ucdavis.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center on Aging, University of Connecticut Health Center, Farmington, CT, United States. Electronic address: kenny@uchc.edu.
authors.forename: Anne
authors.initials: A
authors.lastname: Kenny
authors.affiliation: USDA, ARS, WHNRC, Davis, CA, United States. Electronic address: Theresa.Pedersen@ARS.USDA.GOV.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.affiliation: Metabolon, Inc., Durham, NC, United States. Electronic address: KPappan@metabolon.com.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Pappan
authors.affiliation: Department of Nutrition, University of California, Davis, Davis, CA, United States; USDA, ARS, WHNRC, Davis, CA, United States. Electronic address: John.Newman@ARS.USDA.GOV.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D016000:Cluster Analysis; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D016002:Discriminant Analysis; D063388:Endocannabinoids / Q000097:blood*; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D016018:Least-Squares Analysis; D055442:Metabolome / Q000187:drug effects / Q000235:genetics; D055432:Metabolomics; D054883:Oxylipins / Q000097:blood*; D017698:Postmenopause / Q000097:blood
chemical_list: D000596:Amino Acids; D004041:Dietary Fats; D063388:Endocannabinoids; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D020404:Glycerophospholipids; D054883:Oxylipins
keywords: Endocannabinoids; Global metabolites; Oxylipins; Postmenopausal women