Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor

Br J Pharmacol. 2015 Feb;172(3):910-23. doi: 10.1111/bph.12957. Epub 2014 Dec 15.


Background and purpose: Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage.

Experimental approach: Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS.

Key results: In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4 ) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet.

Conclusions and implications: This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet
  • Fatty Acids, Omega-6 / pharmacology*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / injuries
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / prevention & control*
  • Lipoxins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Formyl Peptide / antagonists & inhibitors*
  • Receptors, Formyl Peptide / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Structure-Activity Relationship


  • Fatty Acids, Omega-6
  • Fpr1 protein, mouse
  • Lipoxins
  • Receptors, Formyl Peptide
  • lipoxin A4