title: Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Inserm, U1043, Toulouse, France; CNRS, U5282, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France; WHRI, Queen Mary University, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Gobbetti
authors.forename: S
authors.initials: S
authors.lastname: Ducheix
authors.forename: P
authors.initials: P
authors.lastname: le Faouder
authors.forename: T
authors.initials: T
authors.lastname: Perez
authors.forename: F
authors.initials: F
authors.lastname: Riols
authors.forename: J
authors.initials: J
authors.lastname: Boue
authors.forename: J
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: M
authors.initials: M
authors.lastname: Dubourdeau
authors.forename: H
authors.initials: H
authors.lastname: Guillou
authors.forename: M
authors.initials: M
authors.lastname: Perretti
authors.forename: N
authors.initials: N
authors.lastname: Vergnolle
authors.forename: N
authors.initials: N
authors.lastname: Cenac
mesh_terms: D000818:Animals; D004032:Diet; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000293:injuries; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D044045:Lipoxins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D043371:Fatty Acids, Omega-6; C469988:Fpr1 protein, mouse; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; C040527:lipoxin A4