title: A metabolomic analysis of two intravenous lipid emulsions in a murine model.
abstract: BACKGROUND
  Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease.
  
  
  METHODS
  We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling.
  
  
  RESULTS
  The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors.
  
  
  CONCLUSIONS
  Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.
authors.affiliation: Department of Surgery and The Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Kalish
authors.forename: Hau D
authors.initials: HD
authors.lastname: Le
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gura
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bistrian
authors.forename: Mark
authors.initials: M
authors.lastname: Puder
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000009:adverse effects; D005227:Fatty Acids / Q000096:biosynthesis; D005228:Fatty Acids, Essential / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D018384:Oxidative Stress; D057947:Parenteral Nutrition Solutions / Q000009:adverse effects; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D008563:Membrane Lipids; D057947:Parenteral Nutrition Solutions; D010743:Phospholipids; D014280:Triglycerides
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