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 O2 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 μg/kg of lipopolysaccharide (Escherichia coli 055:B5); controls received normal saline. At 2 h, hepatocytes were isolated. Hepatocytes were incubated at 37°C with 0.5 mM [1-14C]palmitate or 0.5 mM [1-14C]palmitate plus 10 mM glutamine. After 1 h, the perchloric acid-soluble 14C-radioactivity (representing mainly ketone bodies) and 14CO2 were measured. Hepatocyte O2 consumption from 0.5 mM palmitate was measured with and without 2.5 ng/mL myxothiazol to estimate intramitochondrial O2 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 14CO2 production, or as the sum of acid-soluble radioactivity plus 14CO2 generation. Glutamine significantly increased fatty acid oxidation (acid-soluble radioactivity plus 14CO2) 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 O2 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.