Acute lung injury is reduced in fat-1 mice endogenously synthesizing n-3 fatty acids.
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.
Mayer
Konstantin
K
University of Giessen Lung Center (UGLC), Medical Clinic II, Justus-Liebig-University Giessen, Klinikstr. 36, D-35392 Giessen, Germany. konstantin.mayer@uglc.de.
Kiessling
Almuth
A
Ott
Juliane
J
Schaefer
Martina Barbara
MB
Hecker
Matthias
M
Henneke
Ingrid
I
Schulz
Richard
R
Günther
Andreas
A
Wang
Jingdong
J
Wu
Lijun
L
Roth
Joachim
J
Seeger
Werner
W
Kang
Jing X
JX
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
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