P.86 Metabolism of medium chain fatty acids in man after infusion of an emulsions containing medium chain triglycerides

Abstract

man after infusion of an emulsions containing medium chain triglycerides C. Carneheim 1, L. Hagenfeldt 2, J. Nordenstr6m 2, L. Aanderud 3 and H. Flaatten 3 1Pharmacia Hospital Care, Stockholm, Sweden, 2Huddinge Hospital, Huddinge, Sweden and 3Haukelands Hospital, Bergen, Norway. Aim: The aim of this study was to examine the metabolism of medium chain fatty acids in man after a short intravenous infusion of an emu{sion containing medium and long chain fatty acids. Methods: Healthy volunteers (n = 9) were infused with an emulsion (Vasolipid® 20%, B. Braun Melsungen) containing medium and long chain fatty acids for 6 h (1.0 g triglycerides/kg bw), after fasting overnight. Immediately after, and 18 h after end of infusion plasma samples were drawn. Urine samples were collected during the 24 h test period. Plasma free fatty acids (FFA) were analysed in the blood samples by a gas chromatographic method. Medium chain dicarboxylic acids (DC) in urine and plasma and 3hydroxy fatty acids (3OHFA) in plasma were analysed by gas chromatographymass spectrometry. These results are extracted from a trial where the effect of the structure of the triglycerides was compared and presented as mean _+ SEM. Results: The plasma levels of medium chain fatty acids (C6+C8+C10) were at end of infusion 608 _+ 30 #mol/I for their metabolites DC and 3OHFA 63.0 + 8.8 and 32.4 + 6.6 #mol/I, respectively and returned to zero 18 hours after the end of infusion. The amount fatty acids excreted as DC in urine, 388 + 80 ~mol/24 h, was less than 0.5% of given dose. The relative composition of octanoic (C8) and decanoic (C10) acids detected in plasma at end of infusion reflects the ratio in the emulsion as such. This indicates that there is no specific accumulation of either of the two medium chain fatty acids in plasma. The increase in dicarboxylic acids was mainly due to formation of sebasic acid (DC10). This result suggests a slow removal of C10 from the cytosol and thereby an increase in the formation of DC10 by microsomal w-oxidation. This accumulation may be explained by a carnitine dependency of the uptake of decanoic acid into the mitochondria. For C8 on the other hand, the 3-hydroxyacyI-CoA dehydrogenation appears to be the limiting step leading to leakage of 3OH C8 to plasma. This chain-length may correspond to the minimum of the sum of the activities from shortand longchain 3-hydroxyacyI-CoA dehydrogenase in the mitochondria. The shift in the composition of DC in urine compared to the plasma composition suggests an oxidation of DC10. This is most likely to take place in the peroxisomes.