Fat metabolism during total parenteral nutrition: A biochemical and ultra-structural study

Sammanfattning: This thesis evaluates alterations in lipid metabolism and Kupffer cell morphology seen during total parenteral nutrition in healthy rats. 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. 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 haemophagocytosis 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.