title: Acute lung injury is reduced in fat-1 mice endogenously synthesizing n-3 fatty acids.
abstract: BACKGROUND
  Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency.
  
  
  OBJECTIVE
  To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI.
  
  
  METHODS
  We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice--markers of sickness behavior--were also recorded.
  
  
  RESULTS
  In ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B(2) levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster.
  
  
  CONCLUSIONS
  fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI.
authors.affiliation: University of Giessen Lung Center (UGLC), Medical Clinic II, Justus-Liebig-University Giessen, Klinikstr. 36, D-35392 Giessen, Germany. konstantin.mayer@uglc.de.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mayer
authors.forename: Almuth
authors.initials: A
authors.lastname: Kiessling
authors.forename: Juliane
authors.initials: J
authors.lastname: Ott
authors.forename: Martina Barbara
authors.initials: MB
authors.lastname: Schaefer
authors.forename: Matthias
authors.initials: M
authors.lastname: Hecker
authors.forename: Ingrid
authors.initials: I
authors.lastname: Henneke
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.forename: Jingdong
authors.initials: J
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.forename: Joachim
authors.initials: J
authors.lastname: Roth
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001522:Behavior, Animal; D001831:Body Temperature; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000032:analysis; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D016328:NF-kappa B / Q000378:metabolism; D012121:Respiration, Artificial; D013929:Thromboxane B2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C466741:fat-1 protein, C elegans; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases