Fat metabolism during total parenteral nutrition: a biochemical and ultra‐structural study
Authors: Roth B. 
Published: January 2009

Background: Before the introduction of Intralipid in 1961, the incidence of adverse reactions to intravenous fat emulsions was quite common. Concurrent with hyperlipidaemia, multiple organ dysfunction could occur, but the most prominent symptoms were high fever and anaemia, and the reaction was called “the fat overloading syndrome”. Although the reports are quite rare today the reaction does still appear, and we have observed that some patients develop severe fever during or after incidental retention of exogenous fat in the blood during total parenteral nutrition (TPN). The pathophysiological background to these adverse reactions, as well as the final destiny and the effects of the retained exogenous fat particles, are largely unknown. These questions initiated the present study, which focuses on two factors of importance for the clearance of infused fat from the circulation: the lipoprotein lipase (LPL) system and the reticluloendo‐thelial system.

Methods: An introductory analysis of the clinical course of a head‐injured patient suffering from fat intolerance during TPN implied that observed adverse reactions could be due to influence on macrophages by retained exogenous fat particles.

Results: During infusion of lipid emulsions, cholesterol and phospholipids accumulated in non‐high‐density lipoproteins, while high‐density lipoproteins were enriched in triglycerides. Triglycerides also accumulated in hepatic tissue, and the activity of hepatic lipase decreased.

Although lipoprotein lipase activity in the heart was up‐regulated and serum levels of triglycerides were normal, suggesting that the total elimination rate of triglycerides was not impaired, ultra‐structural investigations indicated that Kupffer cells were involved in clearing exogenous lipids from the blood during the infusion of long‐chain triglycerides. Furthermore, the Kupffer cells were activated, according to morphological criteria. When high doses of fat were given intravenously, the Kupffer cells were grossly distended by fat vacuoles, and serum levels of lactate dehydrogenase increased.

During treatment with fat emulsions containing medium‐chain triglycerides and long‐chain triglycerides in equal amounts, the alterations in lipid transport were less pronounced, and signs of Kupffer cell activation were weaker than during infusion with long‐chain triglycerides only.

Conclusion: The experimental studies showed that infusion of exogenous fat particles interfered with the regulation of lipid transport, and there were signs of increased demands on various aspects of lipid metabolism. Although the capacity of the LPL was sufficient in most situations in healthy rats, the Kupffer cells seemed to be involved in the clearance of exogenous lipids. The present investigations identified one factor, LCT fat emulsion, which was necessary for the appearance of fat vacuoles in the Kupffer cells during TPN.

To some extent, the experimental findings may be related to clinical observations of a head‐injured patient who developed signs of acute, severe macrophage activation with haemophago‐cytosis during and after accumulation of exogenous fat in the blood after treatment with intravenous fat emulsions. The condition was considered to be a consequence of impaired lipid elimination and altered macrophage function during clearance of fat from the blood, a consideration supported by the morphological changes of rat Kupffer cells after TPN in the present study.