P.99 Parenteral nutrition-related liver diseaseand lipid emulsions containing medium chain triglycerides

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.

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

Nutrients ◽

10.3390/nu13020508 ◽

2021 ◽

Vol 13 (2) ◽

pp. 508

Author(s):

Gregory Guthrie ◽

Douglas Burrin

Keyword(s):

Fatty Acid Composition ◽

Parenteral Nutrition ◽

Fish Oil ◽

Lipid Emulsion ◽

Medium Chain Triglyceride ◽

Cholestatic Liver Disease ◽

Lipid Emulsions ◽

Medium Chain Triglycerides ◽

Medium Chain ◽

Life Saving

Total parenteral nutrition (TPN) is a life-saving intervention for infants that are unable to feed by mouth. Infants that remain on TPN for extended periods of time are at risk for the development of liver injury in the form of parenteral nutrition associated cholestasis (PNAC). Current research suggests the lipid component of TPN is a factor in the development of PNAC. Most notably, the fatty acid composition, vitamin E concentration, and presence of phytosterols are believed key mediators of lipid emulsion driven PNAC development. New emulsions comprised of fish oil and medium chain triglycerides show promise for reducing the incidence of PNAC in infants. In this review we will cover the current clinical studies on the benefit of fish oil and medium chain triglyceride containing lipid emulsions on the development of PNAC, the current constituents of lipid emulsions that may modulate the prevalence of PNAC, and potential new supplements to TPN to further reduce the incidence of PNAC.

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Odd-Numbered Medium-Chain Triglycerides (Trinonanoin) in Total Parenteral Nutrition: Effects on Parameters of Fat Metabolism in Rabbits

Journal of Parenteral and Enteral Nutrition ◽

10.1177/0148607193017006522 ◽

1993 ◽

Vol 17 (6) ◽

pp. 522-528 ◽

Cited By ~ 5

Author(s):

Jakob Linseisen ◽

Günther Wolfram

Keyword(s):

Parenteral Nutrition ◽

Total Parenteral Nutrition ◽

Fat Metabolism ◽

Medium Chain Triglycerides ◽

Medium Chain

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The effects of short term lipid infusion on plasma and hepatic bile lipids in humans

Gut ◽

10.1136/gut.45.3.453 ◽

1999 ◽

Vol 45 (3) ◽

pp. 453-458 ◽

Cited By ~ 5

Author(s):

R Pakula ◽

F M Konikoff ◽

A M Moser ◽

F Greif ◽

A Tietz ◽

...

Keyword(s):

Gall Bladder ◽

Lipid Emulsions ◽

Medium Chain Triglycerides ◽

Hepatic Bile ◽

Lipid Infusion ◽

Bile Composition ◽

Medium Chain ◽

Increased Risk ◽

Long Chain Triglycerides ◽

Long Chain

BACKGROUNDPatients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.AIMSTo determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy.METHODSIn eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides.RESULTSLipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions.CONCLUSIONSInfusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.

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