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 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + 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 30:70 FO:MCT 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 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + 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.

• Authors: Meredith A Baker, Bennet S Cho, Lorenzo Anez-Bustillos, Duy T Dao, Amy Pan, Alison A O'Loughlin, Zachary M Lans, Paul D Mitchell, Vania Nosé, Kathleen M Gura, Mark Puder, Gillian L Fell
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 109 Issue 4 Pg. 1038-1050 (04 01 2019) ISSN: 1938-3207 [Electronic] United States
• PMID: 30882140 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © American Society for Nutrition 2019.

Chemical References

• Anti-Inflammatory Agents
• Fat Emulsions, Intravenous
• Fish Oils
• Interleukin-6
• Triglycerides
• Tumor Necrosis Factor-alpha
• alpha-Tocopherol

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry)
• Disease Models, Animal
• Fat Emulsions, Intravenous (administration & dosage, chemistry)
• Fish Oils (administration & dosage, chemistry)
• Humans
• Interleukin-6 (genetics, immunology)
• Liver Diseases (etiology, genetics, immunology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Parenteral Nutrition (adverse effects)
• Triglycerides (administration & dosage, chemistry)
• Tumor Necrosis Factor-alpha (genetics, immunology)
• alpha-Tocopherol (administration & dosage)