Parenteral Soybean Oil Induces Hepatosteatosis Despite Addition of Fish Oil in a Mouse Model of Intestinal Failure-Associated Liver Disease.

Abstract

Replacement of parenteral soybean oil (SO) with fish oil (FO) is an effective therapy for intestinal failure-associated liver disease (IFALD) in children. However, practitioners remain concerned about the risk of essential fatty acid deficiency (EFAD) and sometimes treat IFALD with a combination of 50% SO and 50% FO emulsions. The purpose of this study was to determine if mixing 50% SO and 50% FO emulsions would prevent hepatosteatosis in a murine model of parenteral nutrition (PN)-induced hepatosteatosis. C57BL/6 mice were randomized to receive oral PN with parenteral saline, FO, SO, or a mixture of 50% FO and 50% SO for 19 days. Fatty acid analysis, histologic evaluation, Nonalcoholic Steatohepatitis Clinical Research Network (NSCRN) scores, and reverse-transcriptase polymerase chain reaction for key lipogenic genes were performed. The PN + saline group was the only group with EFAD, with a serum and hepatic triene/tetraene ratio of 0.53. NSCRN scores were highest in the PN + SO group (5.5; 95% confidence interval [CI], 4.9-6.1), followed by the PN + FO/SO (4.5; 95% CI, 3.5-5.5) group, with the lowest score in the PN + FO (2.0; 95% CI, 1.1-2.9) group. Acetyl CoA carboxylase α and acetyl CoA carboxylase β expression was lower in the PN + FO group than in the PN + FO/SO or PN + SO groups. Our data demonstrate that a mixed fat emulsion of 50% SO and 50% FO is inferior to 100% FO in reducing hepatosteatosis in this model. These data suggest that use of parenteral SO with parenteral FO, in a 1:1 ratio, may still contribute to liver injury, although it is less hepatotoxic than pure SO.