Fat metabolism : A clinical and experimental study with special reference to newborns

Abstract: Lipid emulsion is an important constituent of total parenteral nutrition (TPN). In the investigations described in this thesis the effects of different lipid emulsions in neonates were studied.Twenty neonates in each of two studies, undergoing surgery for oesophago-gastrointestinal malformations, were assigned the day after the operation to receive TPN for 5 days, containing one of the two emulsions. In the first study 10 neonates received PFE 4501 containing gamma-linolenic acid (GLA) and carnitine and 10 were given Intralipid®and served as controls. In the second study 10 received Vasolipid® and 10, the control group, Intralipid®. In both studies linoleic acid and α-linolenic acid increased in plasma lipid esters and adipose tissue in each group. Arachidonic acid decreased in the PFE 4501 group in spite of GLA supplementation. Plasma carnitine increased two-fold in the PFE 4501 group, but decreased in the groups receiving Vasolipid® or Intralipid®. Reference ranges for muscle carnitine concentrations in children 1 days to 14 years of age were determined for comparisons. The results showed that the carnitine concentration in skeletal muscle tissue was greatly dependent on the gestational age in newborns. Accumulation of carnitine in skeletal muscle tissue continued during the first year of life, after which the concentration remained essentially constant. There are several methods for determining carnitine concentrations in plasma and muscle, but in the PET camera measurements are made in vivo. The transfer of long-chain fatty acids into the mitochondria, which relies on the carnitine-dependent transport system, was studied with PET, with labelling of the radioactive isotope carbon-11. Inhibition of carnitine palmitoyltransferase I by oxfenicine almost completely blocked the oxidative pathway of palmitic acid, while short carbon-chain fatty acids, which are independent of carnitine for their transport, were virtually unaffected. The fractional oxidative utilisation of long-chain fatty acids may thus be used as an index of the activity of the carnitine-dependent transport system.