title: Parenteral nutrition-associated liver injury and increased GRP94 expression prevented by ω-3 fish oil-based lipid emulsion supplementation.
abstract: OBJECTIVE
  Parenteral nutrition in infants with gastrointestinal disorders can be lifesaving, but it is also associated with parenteral nutrition-associated liver disease. We investigated the effects of incorporating ω-3 fish oil in a parenteral nutrition mixture on signs of parenteral nutrition-associated liver disease and explored the mechanism involved in this process.
  
  
  METHODS
  Seven-day-old New Zealand rabbits were divided into 3 groups of 8, and for 1 week they were infused via the right jugular vein with standard total parenteral nutrition with soybean oil (TPN-soy) or TPN with ω-3 fish oil-based lipid emulsion (TPN-FO), or naturally nursed with rabbit milk (control). Serum and liver tissues were analyzed for serological indicators and pathology, respectively. Reverse-transcriptase polymerase chain reaction was used to evaluate the messenger RNA levels of the endoplasmic reticulum stress chaperone protein glucose-regulated protein 94 (GRP94) in liver tissues and GRP94 protein levels were compared through immunohistochemistry and Western blot assays.
  
  
  RESULTS
  TPN-soy animals had significantly higher serum total bilirubin, direct bilirubin, and γ-glutamyl transpeptidase and lower serum albumin than the controls (P < 0.01, each) or the TPN-FO group, which were similar to the controls (P < 0.01 cf. TPN). Damage to liver tissues of the TPN-FO group was much less than that of the TPN-soy group. GRP94 messenger RNA and protein levels in liver tissues of TPN-soy animals were significantly higher than that of the controls or TPN-FO rabbits, which were similar to the controls.
  
  
  CONCLUSIONS
  Incorporating ω-3 fish oil in parenteral nutrition emulsion greatly prevented liver dysfunction and liver tissue damage in week-old rabbit kits, possibly by preventing endoplasmic reticulum stress.
authors.affiliation: *Department of Neonatology †Institute of Pediatric Research ‡Department of Neonatology Surgery, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xiao
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Chen
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yumin
authors.initials: Y
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D013024:Soybean Oil / Q000008:administration & dosage
chemical_list: D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C018551:glucose-regulated proteins; D013024:Soybean Oil