Abstract

BackgroundArachidonic acid (ARA) is an essential fatty acid and a major constituent of biomembranes. It is converted into various lipid mediators, such as prostaglandin E2 (PGE2) and lipoxin A4 (LXA4). The effects of dietary ARA on colon maintenance are unclear because PGE2 has both mucosal protective and proinflammatory effects, and LXA4 has an anti-inflammatory role. Our objective is to clarify the effects of dietary ARA on an experimental murine colitis model.MethodsC57BL/6 mice were fed three types of ARA diet (0.075%, 0.15% or 0.305% ARA in diet), DHA diet (0.315% DHA) or control diet for 6 weeks, and were then administered dextran sodium sulphate (DSS) for 7 days to induce colitis. We evaluated colitis severity, fatty acid and lipid mediator contents in colonic tissue, and the expression of genes related to lipid mediator formation.ResultsARA composition of colon phospholipids was significantly elevated in an ARA dose-dependent manner. ARA, as well as DHA, did not affect colitis severity (body weight loss, colon shortening, diarrhea and hemoccult phenomena) and histological features. PGE2 contents in the colon were unchanged by dietary ARA, while LXA4 contents increased in an ARA dose-dependent manner. Gene expression of cyclooxygenase (COX)-1 and COX-2 was unchanged, while that of 12/15-lipoxgenase (LOX) was significantly increased by dietary ARA. ARA composition did not correlate with neither colon length nor PGE2 contents, but significantly correlated with LXA4 content.ConclusionThese results suggest that dietary ARA increases ARA and LXA4 contents in colon, but that it has no effect on severity and PGE2 content in a DSS-induced murine colitis model.

Highlights

  • Arachidonic acid (ARA) is an essential fatty acid and a major constituent of biomembranes

  • We recently reported that ARA supplementation increases plasma ARA but does not increase ARAderived lipid mediators or clinical parameters, including inflammation parameters such as C-reactive proteins, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in healthy Japanese elderly individuals [12]

  • In order to clarify the effects of dietary ARA on a murine colitis model, we evaluated the effects of ARA at various doses on colitis severity, determined the contents of ARA and ARA-derived lipid mediators, and assessed the expression of genes related to these lipid mediators

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Summary

Introduction

Arachidonic acid (ARA) is an essential fatty acid and a major constituent of biomembranes. It is converted into various lipid mediators, such as prostaglandin E2 (PGE2) and lipoxin A4 (LXA4). The effects of dietary ARA on colon maintenance are unclear because PGE2 has both mucosal protective and proinflammatory effects, and LXA4 has an anti-inflammatory role. ARA is an n-6 essential fatty acid and is a major constituent of biomembranes. One of its physiological roles is acting as the starting substrate for various lipid mediators, such as prostaglandins (PGs), Colitis is a major inflammatory disease in digestive organs [4]. The effects of ARA and the ARA-derived lipid mediators on colitis are complicated

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