title: Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism.
abstract: Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Male Fischer CDF344 rats fed an adequate LA (5.2 % energy (en)) or low LA (0.4 % en) diet for 15 weeks were infused with LPS (250 ng/h) or vehicle into the fourth ventricle for 2 days using a mini-osmotic pump. The incorporation rate of intravenously infused unesterified14C-AA into brain lipids, eicosanoids, and activities of phospholipase A2and COX-1 and 2 enzymes were measured. Dietary LA lowering reduced the LPS-induced increase in prostaglandin E2concentration and COX-2 activity (P < 0.05 by two-way ANOVA) without altering phospholipase activity. The14C-AA incorporation rate into brain lipids was decreased by dietary LA lowering (P < 0.05 by two-way ANOVA). The present findings suggest that dietary LA lowering reduced LPS-induced increase in brain markers of AA metabolism. The clinical utility of LA lowering in brain disorders should be explored in future studies.
authors.affiliation: Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, One Shields Avenue, Davis, CA, 95616, USA. ataha@ucdavis.edu.
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Helene C
authors.initials: HC
authors.lastname: Blanchard
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yewon
authors.initials: Y
authors.lastname: Cheon
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Epolia
authors.initials: E
authors.lastname: Ramadan
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002247:Carbon Isotopes; D004041:Dietary Fats / Q000494:pharmacology*; D007700:Kinetics; D019787:Linoleic Acid / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D004041:Dietary Fats; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D019787:Linoleic Acid
keywords: Bacterial lipopolysaccharide; Deficiency; Docosahexaenoic acid (DHA); Linoleic acid (LA); Lowering; Neuroinflammation; Omega-3 (n-3); Omega-6 (n-6); Polyunsaturated fatty acids (PUFAs); Ventricle