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

Thomas Gobbetti (1, 2) , Simon Ducheix (3) , Pauline Le Faouder (1, 4, 5) , Teresa Pérez-Berezo (1) , Fabien Riols (5, 4) , Jérôme Boué (1) , Justine Bertrand-Michel (5, 4) , Marc Dubourdeau (6) , Hervé Guillou (7) , Mauro Perretti (2) , Nathalie Vergnolle (1, 2) , Nicolas Cenac (1, 2)

1 CPTP - Centre de Physiopathologie Toulouse Purpan
2 WHRI
3 ToxAlim - ToxAlim
4 MetaToul Lipidomics
5 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
6 Ambiotis - Ambiotis
7 ToxAlim-TIM - Toxicologie Intégrative & Métabolisme

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. 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. 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. 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.

Mots clés: fatty acid; polyunsaturated fatty acid; reperfusion injury; intussusception

Mots clés: acide gras; acide gras polyinsaturé; acide gras polyinsaturé n 6; acide gras polyinsaturé n-3; régime alimentaire; ischémie reperfusion; maladie intestinale; appareil intestinal

Domaines: Sciences du Vivant [q-bio]

Thomas Gobbetti, Simon Ducheix, Pauline Le Faouder, Teresa Pérez-Berezo, Fabien Riols, et al.. Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor. British Journal of Pharmacology, 2015, 172 (3), pp.910-923. ⟨10.1111/bph.12957⟩. ⟨hal-01601458⟩