Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution

Abstract

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

Evaluation of SMOFlipid in Pediatric Intestinal‐Failure Patients and Its Effects on Essential Fatty Acid Levels

“…Our results showed statistically significant improvements in GGT and ALT 1.5 years after transitioning to SMOFlipid, supporting previously published literature showing minimal hepatic effects or development of IFALD following transition to SMOFlipid 5,13,19‐21 . Prior studies have demonstrated conflicting data on SMOFlipid effects on hepatic enzyme trends.…”

Impact of Parenteral Lipid Emulsion Components on Cholestatic Liver Disease in Neonates

“…In adult mouse models, mice that are enterally fed PN solution containing amino acids and glucose while being administered SO-LE intravenously rapidly develop hepatic steatosis [ 69 , 70 , 71 , 72 , 73 ]. The administration of FO-LE does not lead to steatosis in this model [ 71 , 73 ].…”

“…Fell et at. administered vitamin E supplemented SO-LE enterally to adult mice which prevented steatosis and maintained healthy hepatic architecture compared to regular SO-LE [ 70 ]. In a similar study, enteral administration of FO-LE was supplemented with vitamin E for 19 days [ 30 ].…”

The effects and safety of omega-3 fatty for acute lung injury: a systematic review and meta-analysis

“…At present, the fat emulsions used in clinical practice are mostly based on soybean oil. Soybean oil-based fat emulsions are rich in long-chain fat emulsions, which can affect granulocyte activity under severe stress such as trauma and infection, resulting in impaired immune function and increased lipid peroxidation, which in turn increases organ function damage [ 10 , 11 ]. This tendency to increase the inflammatory response often makes the use of soybean oil-based fat emulsions in a dilemma clinically.…”