Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats.
Sepsis or endotoxaemia inhibits gluconeogenesis from various substrates, the main effect being related to a change in the phosphoenolpyruvate carboxykinase transcription rate. In addition, sepsis has been reported to affect the oxidative phosphorylation pathway. We have studied glycerol metabolism in hepatocytes isolated from rats fasted and injected 16 h previously with lipopolysaccharide from Escherichia coli. Endotoxin inhibited glycerol metabolism and led to a very large accumulation of glycerol 3-phosphate; the cytosolic reducing state was increased. Furthermore glycerol kinase activity was increased by 33% (P<<0.01). The respiratory rate of intact cells was significantly decreased by sepsis, with glycerol or octanoate as exogenous substrates, whereas oxidative phosphorylation (ATP-to-O ratio or respirations in state 4, state 3 and the oligomycin-insensitive state as well as the uncoupled state) was unchanged in permeabilized hepatocytes. Hence the effect on energy metabolism seems to be present only in intact hepatocytes. An additional important feature was the observation of a significant increase in cellular volume in cells from endotoxic animals, which might account for the alterations induced by sepsis.
Leclercq
P
P
Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Bâtiment 72 Biologie, BP 53X, 38041 Grenoble-Cedex 09, France.
Filippi
C
C
Sibille
B
B
Hamant
S
S
Keriel
C
C
Leverve
X M
XM
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004099:Dihydroxyacetone Phosphate / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism*; D005994:Glycerophosphates / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D002210:Caprylates; D005994:Glycerophosphates; D008070:Lipopolysaccharides; D019344:Lactic Acid; D004099:Dihydroxyacetone Phosphate; D019289:Pyruvic Acid; C029620:alpha-glycerophosphoric acid; C031492:octanoic acid; D005990:Glycerol