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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 unesterified 14C-AA into brain lipids, eicosanoids, and activities of phospholipase A2 and COX-1 and 2 enzymes were measured. Dietary LA lowering reduced the LPS-induced increase in prostaglandin E2 concentration and COX-2 activity (P < 0.05 by two-way ANOVA) without altering phospholipase activity. The 14C-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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Taha AY,Blanchard HC,Cheon Y,Ramadan E,Chen M,Chang L,Rapoport SI

doi

10.1007/s12035-016-9968-1

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

4303-4315

issue

6

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-016-9968-1

journal_volume

54

pub_type

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