Parenteral Nutrition–Associated Liver Injury and Increased GRP94 Expression Prevented by ω‐3 Fish Oil–Based Lipid Emulsion Supplementation

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.