Fish oil-based injectable lipid emulsions containing medium-chain triglycerides or added α-tocopherol offer anti-inflammatory benefits in a murine model of parenteral nutrition-induced liver injury.

ABSTRACT

BACKGROUND: Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties. OBJECTIVE: The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice. METHODS: A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 5050 FOMCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 5050 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6). RESULTS: All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 3070 FOMCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 5050 FOMCT, 3070 FOMCT, FO + AT, and 5050 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls. CONCLUSIONS: Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.