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.

Gillian L Fell,Duy T Dao,Prathima Nandivada,Amy Pan,Meredith A Baker,Kathleen M Gura,Vania Nose,Alison A O’Loughlin,Bennet S Cho,Lorenzo Anez-Bustillos,Mark Puder,Wolf-Hagen Schunck

doi:10.1371/journal.pone.0217155

Gillian L Fell, Duy T Dao + Show 10 more

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https://doi.org/10.1371/journal.pone.0217155

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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.

Highlights

Parenteral nutrition (PN) is the intravenous administration of macronutrients and micronutrients, including carbohydrates, protein in the form of amino acids, lipids, vitamins, and trace elements
We have found that the fish oil emulsion (FO) and soybean oil emulsion (SO) made in the laboratory have the same effects on the liver as their commercial counterparts in a murine model of parenteral nutrition (PN)-induced liver injury (S1 Fig)
Alpha-tocopherol levels in the emulsions formulated with FO, fish oil containing phytosterols (FO+P), and soybean oil containing αtocopherol (SO+AT) were comparable

Summary

Introduction

Parenteral nutrition (PN) is the intravenous administration of macronutrients and micronutrients, including carbohydrates, protein in the form of amino acids, lipids, vitamins, and trace elements. PN is life sustaining for IF patients, there are complications associated with its administration. One such complication is the development of intestinal failure-associated liver disease (IFALD), which is characterized by cholestatic liver disease that can progress to cirrhosis and end-stage liver disease necessitating liver transplantation. It has been demonstrated that use of fish oil as a parenteral fat source can prevent PN-induced liver injury in animal models [1,2] and reverse cholestasis and stop or slow the progression of liver disease in patients with IFALD [3,4,5,6,7,8,9]

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