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Effect of intravenous lipid emulsions on hepatic cholesterol metabolism
P D Whitfield1, P T Clayton, D P Muller
1Biochemistry, Endocrinology, and Metabolism Unit, Institute of Child Health, University College London, United Kingdom.
Insights
Intravenous lipid emulsions used in total parenteral nutrition may disrupt infant liver cholesterol metabolism. This finding could explain the development of liver complications in infants receiving this life-saving therapy.
Area of Science:
- Biochemistry
- Hepatology
- Neonatal Medicine
Background:
- Total parenteral nutrition (TPN) is crucial for infants with gut failure but is linked to cholestatic liver disease.
- The exact causes of TPN-associated liver complications in infants are unknown.
- Lipid emulsions in TPN are suspected contributors to these adverse effects.
Purpose of the Study:
- To investigate the impact of lipid emulsions on hepatic cholesterol metabolism in vitro.
- To explore potential mechanisms behind TPN-associated liver issues.
Main Methods:
- Development of an in vitro system using cultured hepatocytes (Hep G2 cells).
- Exposure of cells to Intralipid, a common lipid emulsion.
Main Results:
- Intralipid significantly inhibited cholesterol uptake by Hep G2 cells in a dose-dependent and reversible manner.
- Intralipid also promoted cholesterol efflux from the cells.
- The specific components and mechanisms responsible for these effects are yet to be identified.
Conclusions:
- Intravenous lipid emulsions can interfere with hepatic cholesterol metabolism.
- This interference may play a role in the pathogenesis of TPN-associated cholestasis in neonates.
Background:
Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible.
Methods:
An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes.
Results:
Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose-dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established.
Conclusions:
Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition-associated cholestasis in neonates.