Fatty acid oxidation in neonatal hepatocytes: effects of sepsis and glutamine.
OBJECTIVE
Little is known about fat use during sepsis during the neonatal period. Intramitochondrial O(2) consumption is inhibited in isolated hepatocytes from suckling septic rats and this impairment is reversed by glutamine. We investigated the effect of neonatal sepsis on fat oxidation and whether glutamine can directly affect fatty acid oxidation.


METHODS
Suckling Wistar rats (11 d) received an intraperitoneal injection of 300 microg/kg of lipopolysaccharide (Escherichia coli 055:B5); controls received normal saline. At 2 h, hepatocytes were isolated. Hepatocytes were incubated at 37 degrees C with 0.5 mM [1-(14)C]palmitate or 0.5 mM [1-(14)C]palmitate plus 10 mM glutamine. After 1 h, the perchloric acid-soluble (14)C-radioactivity (representing mainly ketone bodies) and (14)CO(2) were measured. Hepatocyte O(2) consumption from 0.5 mM palmitate was measured with and without 2.5 ng/mL myxothiazol to estimate intramitochondrial O(2) consumption.


RESULTS
There were no significant differences in fatty acid oxidation between control and endotoxemic hepatocytes measured as acid-soluble radioactivity (which represents mainly ketogenesis, plus Krebs cycle intermediates), as (14)CO(2) production, or as the sum of acid-soluble radioactivity plus (14)CO(2) generation. Glutamine significantly increased fatty acid oxidation (acid-soluble radioactivity plus (14)CO(2)) in hepatocytes from control and endotoxic animals.


CONCLUSIONS
The finding of no significant difference in fatty acid oxidation between hepatocytes from control and endotoxemic rats is surprising given that intramitochondrial O(2) consumption from palmitate is decreased. This may reflect altered use of acetyl-coenzyme A to ketone bodies and Krebs cycle intermediates. Glutamine enhanced fatty acid oxidation from control and endotoxemic hepatocytes, suggesting that it may promote substrate oxidation during endotoxemia.
Kim
Seong Chul
SC
Department of Paediatric Surgery, Institute of Child Health, Great Ormond Street Hospital, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Pierro
Agostino
A
Zamparelli
Marcello
M
Spitz
Lewis
L
Eaton
Simon
S
D000818:Animals; D000831:Animals, Newborn; D005227:Fatty Acids / Q000378:metabolism*; D005973:Glutamine / Q000627:therapeutic use*; D022781:Hepatocytes / Q000502:physiology*; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000473:pathology*
D005227:Fatty Acids; D008070:Lipopolysaccharides; D005973:Glutamine