Parenteral nutrition-associated liver injury and increased GRP94 expression prevented by ω-3 fish oil-based lipid emulsion supplementation

J Pediatr Gastroenterol Nutr. 2014 Dec;59(6):708-13. doi: 10.1097/MPG.0000000000000558.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dietary Supplements
  • Disease Models, Animal
  • Fat Emulsions, Intravenous / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Fish Oils / administration & dosage
  • Gene Expression / drug effects*
  • HSP70 Heat-Shock Proteins / analysis
  • HSP70 Heat-Shock Proteins / genetics*
  • Liver / chemistry
  • Liver / pathology
  • Liver Diseases / etiology*
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Parenteral Nutrition, Total / adverse effects*
  • RNA, Messenger / analysis
  • Rabbits
  • Soybean Oil / administration & dosage

Substances

  • Fat Emulsions, Intravenous
  • Fatty Acids, Omega-3
  • Fish Oils
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • RNA, Messenger
  • glucose-regulated proteins
  • Soybean Oil