title: Molecular impact of omega 3 fatty acids on lipopolysaccharide-mediated liver damage.
abstract: BACKGROUND
  Growing evidence suggests that omega 3 fatty acid containing lipid emulsions have a beneficial effect on parenteral nutrition associated liver disease (PNALD). However, the cellular and molecular mechanisms responsible for this effect are unclear. In this study, we investigated whether Omegaven™ fish oil emulsion could inhibit lipopolysaccharidase (LPS) mediated liver damage.
  
  
  METHODS
  We examined the effects of Omegaven™ and LPS alone and synergistically on hepatic paraoxonase 1 (PON1), a potent antioxidant protein, ERK1/2 activity, and TLR4 regulation.
  
  
  RESULTS
  LPS did not alter PON1 release from HepG2 cells but did significantly decrease PON1 protein synthesis (44%, P<0.05). Omegaven™ alone had no direct effect on PON1 release. However, it did significantly reverse LPS-mediated decrease in PON1 protein levels (control: 100%; LPS alone: 56+/4%; LPS+Omegaven™: 87+/6%, P<0.05). Furthermore, molecular analysis indicated that Omegaven™ blocked LPS-mediated increase in ERK1/2 activity (35% increase), an important LPS signal transduction pathway. TLR4, the receptor for LPS, was down-regulated in the presence of Omegaven™.
  
  
  CONCLUSIONS
  Omegaven™ may be beneficial in patients with PNAC because of its ability to reverse LPS-mediated inhibition of antioxidant promoting PON1 expression, and this activity may be in part mediated by the ERK1/2 pathway.
authors.affiliation: Department of Surgery, State University of New York at Buffalo, Buffalo, NY.
authors.forename: George
authors.initials: G
authors.lastname: Ventro
authors.affiliation: Department of Surgery, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Surgery, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Yingkui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Surgery, State University of New York at Buffalo, Buffalo, NY. Electronic address: charmon@kaleidahealth.org.
authors.forename: Carroll M
authors.initials: CM
authors.lastname: Harmon
mesh_terms: D043303:Aryldialkylphosphatase / Q000378:metabolism; D045744:Cell Line, Tumor; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: LPS; Lipopolysaccharide; PON1; Parenteral nutrition; TPN